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Chronic Stress and Energy Balance: Role of the Hypothalamo‐Pituitary‐Adrenal Axis

Mary F. Dallman, Seema Bhatnagar

10.1002/cphy.cp070410

Source: Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Regulation of Function in the Hypothalamo‐Pituitary‐Adrenal Axis
1.1 Corticosteroid Receptors: Feedback Control of the Hypothalamo‐Pituitary‐Adrenal Axis by Exogenous Corticosteroid Treatment
1.2 Stressor‐Induced Endogenous Corticosteroid Secretion and Feedback Control
1.3 Chronic or Repeated Stressors Induce Facilitated Responses
1.4 Diurnal Rhythms and Responsivity
2 Acute Versus Chronic Stressors: Effects on Activity in the Hypothalamo‐Pituitary‐Adrenal Axis
2.1 Acute Responses to Stress
2.2 Adaptations to Intermittent Stimuli
2.3 Adaption to Chronic, Sustained Stimuli
3 Corticosteroids, Stress, and Energy Balance
3.1 Energy Acquisition
3.2 Energy Disposition
4 Chronic Stress in Humans
Figure 1. Figure 1.

The circadian excursion in corticosterone adjusts to exogenous steroid. A: A typical circadian rhythm in plasma corticosterone in rats provided 5 days previously with a subcutaneous wax pellet (control, solid lines and symbols). Trough values occur at lights‐on and peak values at lights‐off. A subcutaneous corticosterone pellet was provided 5 days previously that caused plasma corticosterone concentrations of 4 μg/dl at lights‐on (exogenous B, dashed lines, open symbols). Elevations in trough corticosterone levels cause the Hypothalamo‐Pituitary‐Adrenal axis to reduce endogenous corticotropin secretion so that the mean 24 h corticosterone level in both groups is ∼5 μg/dl. B: Treatment of rats with 20%, 40%, or 80% corticosterone in 100 mg pellets containing corticosterone:cholesterol (w/w) 5 days previously causes graded increases in plasma corticosterone concentrations measured in the morning within 1 h of lights‐on. At the right is an estimate of the circulating total corticosterone concentrations (both free and bound to transcortin) that are sufficient to occupy the mineralocorticoid receptor (MR) and both the mineralocorticoid and glucocorticoid receptors (GR). Although the graph stops at 10 μg/dl, this is just the lower part of the dynamic range of plasma corticosterone, which extends to at least 60 μg/dl.

From Akana et al. 8, with permission
Figure 2. Figure 2.

Effects of elevations in trough plasma corticosterone by implantation of pellets 5 days previously. Biological effects of elevated trough corticosterone concentrations on end points within the Hypothalamo‐Pituitary‐Adrenal axis are more sensitive to small increases in corticosterone (left panels, adrenal weight and stress‐induced corticotropin concentrations) than are end points in other systems (right panels, thymus and body weights). Central feedback regulation of the Hypothalamo‐Pituitary‐Adrenal axis by occupancy of both mineralocorticoid (MR) and glucocorticoid (GR) receptors confers greater sensitivity to corticosterone than is exhibited by the peripheral targets of corticosterone. ACTH, corticotropin; BW, body weight.

From Akana et al. 8, with permission
Figure 3. Figure 3.

The plasma corticotropin (ACTH) response to restraint stress exhibits similar temporal dynamics in intact rats and in adrenalectomized (ADX) rats with clamped, steady‐state corticosterone concentrations, showing that changes in corticosterone in response to stress do not acutely alter corticotropin secretion.

From Viau et al. 271, with permission
Figure 4. Figure 4.

Facilitation of corticotropin (ACTH) responses to acute stress occurs in chronically stressed rats. Rats were exposed to cold (5° C) or remained at room temperature (control) for 5 days and then were acutely restrained in the morning of day 5. Intact rats (left) had corticotropin responses of equal magnitude (P = not significant) whether or not they had been chronically exposed to cold stress. Adrenalectomized rats, replaced with a constant corticosterone signal of ∼6 μg/dl (right), had significantly greater corticotropin responses to restraint (P < 0.001) if they had been chronically exposed to cold. Constraining corticosterone in the control and cold groups makes the facilitated corticotropin responses in the chronically stressed rats apparent.

From Akana et al. 6, with permission
Figure 5. Figure 5.

Effect of clamped corticosterone levels in adrenalectomized rats on plasma corticosterone, insulin, and triglyceride concentrations. Corticosterone pellet composition was chosen to provide moderate (near normal) and high plasma concentrations. Corticosterone had a marked dose‐related stimulatory effect on insulin in control rats and inhibited insulin in rats made diabetic with streptozotocin. Triglycerides increased with corticosterone in control rats, and the increase was markedly exacerbated in the diabetics.

From Strack et al. 257, with permission
Figure 6. Figure 6.

Reciprocal interactions between corticosterone and insulin on food intake but not body weight. A: Effects of corticosterone. All rats were adrenalectomized, and half were made diabetic with streptozotocin and studied 5 days later (same rats as in Fig. 5). In nondiabetic rats, both corticosterone pellets increased food intake equally; by contrast, in diabetic rats, in the absence of insulin secretion, there was a marked corticosterone dose‐related increase in food intake, with intake/body weight (BW) more than doubling at the higher dose of corticosterone (top). Body weight was initially the same in all groups, and only the high (80%) corticosterone dose resulted in a significant decrease in weight gain (bottom). B: Effects of insulin. All rats were adrenalectomized and made diabetic with streptozotocin; half were replaced with a moderate (40%) and half with a high (80%) corticosterone pellet. Low doses of insulin (which did not reduce plasma glucose below a mean of 300 mg/dl) were infused by minipump, and the rats were studied 5 days later. Both doses of insulin reduced food intake in the moderate steroid group (P < 0.05), and only the higher dose of insulin reduced food intake in the high steroid group (P < 0.05). Initial body weight was the same in all groups, and at these low doses, insulin infusion had no significant effect on body weight.

From Strack et al. 257, with permission
Figure 7. Figure 7.

The interaction between corticosterone and insulin on the weight of white adipose tissue (WAT) depots is site‐selective (data from the same rats as in Figs. 5 and 6). There is no interaction between the hormones on caloric efficiency; corticosterone inhibits and insulin promotes caloric efficiency (top). Epididymal fat pads increase in weight in a corticosterone dose‐related manner in the presence of insulin and decrease in weight in a dose‐related manner in the absence of insulin. Perirenal fat pads significantly increase or decrease in weight only at the high dose of corticosterone. The magnitude of the increase in perirenal fat weight is 2.5‐fold compared to a 0.5‐fold increase in epididymal fat weight at the same dose of corticosterone. At constant body weight (BW), accrual of fat represents a shift in caloric storage sites in the rats treated with high corticosterone in the presence of high insulin.

From Strack et al. 257, with permission
Figure 8. Figure 8.

Effect of insulin infusion in adrenalectomized, corticosterone‐treated, diabetic rats depends on the dose of corticosterone and is site‐selective on white adipose tissue (WAT) depots. A maximal effect of insulin on caloric efficiency was achieved at the lower dose in rats with moderate (40%) corticosterone pellets. By contrast, caloric efficiency increased with increasing insulin infusion rate in the high (80%) corticosterone pellet group. Insulin infusion rate had a greater effect on epididymal fat weight in the high‐dose steroid group than the medium‐dose group, again showing the marked positive interaction between the hormones on fat deposition. Although insulin increased perirenal adipose depot weight in a dose‐related fashion in rats with moderate corticosterone, the highest rate of insulin infusion was required to increase perirenal adipose weight in rats with high corticosterone, again showing a differential effect of the steroids on intraabdominal compared to more peripheral fat depots. BW, body weight.

From Strack et al. 257, with permission
Figure 9. Figure 9.

Effects of stimulus‐induced increases in endogenous corticosterone secretion on epididymal (eWAT) and perirenal (pWAT) white adipose tissue depots under conditions of concurrently low (A) and high (B) plasma insulin concentrations. A: Rats were placed in cold (5° C) for 5 days or remained at room temperature (control). Although corticosterone secretion was stimulated, insulin was inhibited in the cold‐exposed rats, which lost weight and fat mass; the relative loss in perirenal fat is greater than that in epididymal fat mass. B: Rats were prepared with intracerebroventricular (icv) cannulae and Ginfused for 5 days with either neuropeptide Y (NPY, 6 μg/day) or artificial cerebrospinal fluid (aCSF). Both corticosterone and insulin were stimulated by NPY infusion, and the rats increased food intake and fat mass; the relative gain in perirenal fat is greater than that in epididymal fat mass. BW, body weight.

From Akana et al. 6, with permission


Figure 1.

The circadian excursion in corticosterone adjusts to exogenous steroid. A: A typical circadian rhythm in plasma corticosterone in rats provided 5 days previously with a subcutaneous wax pellet (control, solid lines and symbols). Trough values occur at lights‐on and peak values at lights‐off. A subcutaneous corticosterone pellet was provided 5 days previously that caused plasma corticosterone concentrations of 4 μg/dl at lights‐on (exogenous B, dashed lines, open symbols). Elevations in trough corticosterone levels cause the Hypothalamo‐Pituitary‐Adrenal axis to reduce endogenous corticotropin secretion so that the mean 24 h corticosterone level in both groups is ∼5 μg/dl. B: Treatment of rats with 20%, 40%, or 80% corticosterone in 100 mg pellets containing corticosterone:cholesterol (w/w) 5 days previously causes graded increases in plasma corticosterone concentrations measured in the morning within 1 h of lights‐on. At the right is an estimate of the circulating total corticosterone concentrations (both free and bound to transcortin) that are sufficient to occupy the mineralocorticoid receptor (MR) and both the mineralocorticoid and glucocorticoid receptors (GR). Although the graph stops at 10 μg/dl, this is just the lower part of the dynamic range of plasma corticosterone, which extends to at least 60 μg/dl.

From Akana et al. 8, with permission


Figure 2.

Effects of elevations in trough plasma corticosterone by implantation of pellets 5 days previously. Biological effects of elevated trough corticosterone concentrations on end points within the Hypothalamo‐Pituitary‐Adrenal axis are more sensitive to small increases in corticosterone (left panels, adrenal weight and stress‐induced corticotropin concentrations) than are end points in other systems (right panels, thymus and body weights). Central feedback regulation of the Hypothalamo‐Pituitary‐Adrenal axis by occupancy of both mineralocorticoid (MR) and glucocorticoid (GR) receptors confers greater sensitivity to corticosterone than is exhibited by the peripheral targets of corticosterone. ACTH, corticotropin; BW, body weight.

From Akana et al. 8, with permission


Figure 3.

The plasma corticotropin (ACTH) response to restraint stress exhibits similar temporal dynamics in intact rats and in adrenalectomized (ADX) rats with clamped, steady‐state corticosterone concentrations, showing that changes in corticosterone in response to stress do not acutely alter corticotropin secretion.

From Viau et al. 271, with permission


Figure 4.

Facilitation of corticotropin (ACTH) responses to acute stress occurs in chronically stressed rats. Rats were exposed to cold (5° C) or remained at room temperature (control) for 5 days and then were acutely restrained in the morning of day 5. Intact rats (left) had corticotropin responses of equal magnitude (P = not significant) whether or not they had been chronically exposed to cold stress. Adrenalectomized rats, replaced with a constant corticosterone signal of ∼6 μg/dl (right), had significantly greater corticotropin responses to restraint (P < 0.001) if they had been chronically exposed to cold. Constraining corticosterone in the control and cold groups makes the facilitated corticotropin responses in the chronically stressed rats apparent.

From Akana et al. 6, with permission


Figure 5.

Effect of clamped corticosterone levels in adrenalectomized rats on plasma corticosterone, insulin, and triglyceride concentrations. Corticosterone pellet composition was chosen to provide moderate (near normal) and high plasma concentrations. Corticosterone had a marked dose‐related stimulatory effect on insulin in control rats and inhibited insulin in rats made diabetic with streptozotocin. Triglycerides increased with corticosterone in control rats, and the increase was markedly exacerbated in the diabetics.

From Strack et al. 257, with permission


Figure 6.

Reciprocal interactions between corticosterone and insulin on food intake but not body weight. A: Effects of corticosterone. All rats were adrenalectomized, and half were made diabetic with streptozotocin and studied 5 days later (same rats as in Fig. 5). In nondiabetic rats, both corticosterone pellets increased food intake equally; by contrast, in diabetic rats, in the absence of insulin secretion, there was a marked corticosterone dose‐related increase in food intake, with intake/body weight (BW) more than doubling at the higher dose of corticosterone (top). Body weight was initially the same in all groups, and only the high (80%) corticosterone dose resulted in a significant decrease in weight gain (bottom). B: Effects of insulin. All rats were adrenalectomized and made diabetic with streptozotocin; half were replaced with a moderate (40%) and half with a high (80%) corticosterone pellet. Low doses of insulin (which did not reduce plasma glucose below a mean of 300 mg/dl) were infused by minipump, and the rats were studied 5 days later. Both doses of insulin reduced food intake in the moderate steroid group (P < 0.05), and only the higher dose of insulin reduced food intake in the high steroid group (P < 0.05). Initial body weight was the same in all groups, and at these low doses, insulin infusion had no significant effect on body weight.

From Strack et al. 257, with permission


Figure 7.

The interaction between corticosterone and insulin on the weight of white adipose tissue (WAT) depots is site‐selective (data from the same rats as in Figs. 5 and 6). There is no interaction between the hormones on caloric efficiency; corticosterone inhibits and insulin promotes caloric efficiency (top). Epididymal fat pads increase in weight in a corticosterone dose‐related manner in the presence of insulin and decrease in weight in a dose‐related manner in the absence of insulin. Perirenal fat pads significantly increase or decrease in weight only at the high dose of corticosterone. The magnitude of the increase in perirenal fat weight is 2.5‐fold compared to a 0.5‐fold increase in epididymal fat weight at the same dose of corticosterone. At constant body weight (BW), accrual of fat represents a shift in caloric storage sites in the rats treated with high corticosterone in the presence of high insulin.

From Strack et al. 257, with permission


Figure 8.

Effect of insulin infusion in adrenalectomized, corticosterone‐treated, diabetic rats depends on the dose of corticosterone and is site‐selective on white adipose tissue (WAT) depots. A maximal effect of insulin on caloric efficiency was achieved at the lower dose in rats with moderate (40%) corticosterone pellets. By contrast, caloric efficiency increased with increasing insulin infusion rate in the high (80%) corticosterone pellet group. Insulin infusion rate had a greater effect on epididymal fat weight in the high‐dose steroid group than the medium‐dose group, again showing the marked positive interaction between the hormones on fat deposition. Although insulin increased perirenal adipose depot weight in a dose‐related fashion in rats with moderate corticosterone, the highest rate of insulin infusion was required to increase perirenal adipose weight in rats with high corticosterone, again showing a differential effect of the steroids on intraabdominal compared to more peripheral fat depots. BW, body weight.

From Strack et al. 257, with permission


Figure 9.

Effects of stimulus‐induced increases in endogenous corticosterone secretion on epididymal (eWAT) and perirenal (pWAT) white adipose tissue depots under conditions of concurrently low (A) and high (B) plasma insulin concentrations. A: Rats were placed in cold (5° C) for 5 days or remained at room temperature (control). Although corticosterone secretion was stimulated, insulin was inhibited in the cold‐exposed rats, which lost weight and fat mass; the relative loss in perirenal fat is greater than that in epididymal fat mass. B: Rats were prepared with intracerebroventricular (icv) cannulae and Ginfused for 5 days with either neuropeptide Y (NPY, 6 μg/day) or artificial cerebrospinal fluid (aCSF). Both corticosterone and insulin were stimulated by NPY infusion, and the rats increased food intake and fat mass; the relative gain in perirenal fat is greater than that in epididymal fat mass. BW, body weight.

From Akana et al. 6, with permission
References
 1. Aguilera, G. Regulation of pituitary ACTH during chronic stress. Front. Neuroendocrinol. 15: 321–350, 1994.
 2. Ahima, R. S., D. Prabakaran, C. Mantzoros, D. Qu, B. Lowell, E. Maratos‐Flier, and J. S. Flier. Role of leptin in the neuroendocrine response to fasting. Nature 382: 250–253, 1996.
 3. deleted.
 4. Akana, S. F., and M. F. Dallman. Chronic cold in adrenalectomized, corticosterone (B)‐treated rats: facilitated corticotropin responses to acute stress emerge as B increases. Endocrinology 138: 3249–3258, 1997.
 5. Akana, S. F., and M. F. Dallman. Feedback and facilitation in the adrenocortical system: unmasking facilitation by partial inhibition of the glucocorticoid response to prior stress. Endocrinology 131: 57–68, 1992.
 6. Akana, S. F., E. S. Hanson, C. J. Horsley, A. M. Strack, S. Bhatnagar, M. J. Bradbury, E. D. Milligan, and M. F. Dallman. Clamped corticosterone (B) reveals the effect of endogenous B on both facilitated responsivity to acute restraint and metabolic responses to chronic stress. Stress 1: 33–49, 1996.
 7. Akana, S. F., L. Jacobson, C. S. Cascio, J. Shinsako, and M. F. Dallman. Constant corticosterone replacement normalizes basal adrenocorticotropin (ACTH) but permits sustained ACTH hypersecretion in adrenalectomized rats. Endocrinology 122: 1337–1342, 1988.
 8. Akana, S. F., K. A. Scribner, M. J. Bradbury, A. M. Strack, C.‐D. Walker, and M. F. Dallman. Feedback sensitivity of the rat hypothalamic‐pituitary adrenal axis and its capacity to adjust to exogenous corticosterone. Endocrinology 131: 585–594, 1992.
 9. Akana, S. F., A. M. Strack, E. S. Hanson, and M. F. Dallman. Regulation of activity in the hypothalamo‐pituitary‐adrenal axis is integral to a larger hypothalamic system that determines caloric flow. Endocrinology 135: 1125–1134, 1994.
 10. Albeck, D. S., N. B. Hastings, and B. S. McEwen. Effects of adrenalectomy and type I or type II glucocorticoid receptor activation on AVP and CRH mRNA in the rat hypothalamus. Mol. Brain Res. 26: 129–134, 1994.
 11. Antoni, F. A. Hypothalamic control of adrenocorticotropin secretion: advances since the discovery of 41‐residue corticotropin‐releasing factor. Endocr. Rev. 7: 351–378, 1986.
 12. Arimura, A., S. Takashige, and A. V. Schally. Assays for corticotropin‐releasing factor (CRF) using rats treated wtih morphine, chlorpromazine, dexamethasone and nembutal. Endocrinology 81: 235, 1967.
 13. Arner, P., L. Hellström, H. Wahrenberg, and M. Brönnegård. Beta‐adrenoceptor expression in human fat cells from different regions. J. Clin. Invest. 86: 1595–1600, 1991.
 14. Ashby, P., and D. S. Robinson. Effects of insulin, glucocorticoids and adrenaline on the activity of rat adipose‐tissue lipoprotein lipase. Biochem. J. 188: 185–192, 1980.
 15. Bamberger, C. M., H. M. Schulte, and G. P. Ghrousos. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr. Rev. 17: 245–261, 1996.
 16. Bartanusz, V., D. Jezova, L. T. Bertinin, F. J. H. Tilders, J.‐M. Aubry, and J. Z. Kiss. Stress‐induced increases in vasopressin and corticotropin‐releasing factor expression in hypophysiotropic paraventricular neurons. Endocrinology 132: 895–902, 1993.
 17. Bartness, T. J., C. J. Billington, A. S. Levine, J. E. Morley, N. E. Rowland, and D. M. Brown. Insulin and metabolic efficiency in rats. II. Effects of NE and cold exposure. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R1118–R1125, 1986.
 18. Beltt, B. M., and R. E. Keesey. Hypothalamic map of stimulation current thresholds for inhibition of feeding in rats. Am. J. Physiol. 229: 1124–1133, 1975.
 19. Beneke, W. M., S. E. Schulte, and J. G. Vander Tuig. An analysis of excessive running in the development of activity anorexia. Physiol. Behav. 58: 451–457, 1995.
 20. Berga, K. L., J. F. Mortola, L. Girton, B. Suh, G. Laughlin, P. Pham, and K.S.C. Yen. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J. Clin. Endocrinol. Metab. 68: 301–308, 1989.
 21. Bernardis, L. L. Hypophagia, hypodipsia, and hypoactivity following electrolytic lesions in the dorsomedial nuclei of mature rats of both sexes. J. Neural Transm. 33: 1–10, 1972.
 22. Bernardis, L. L., and L. L. Bellinger. The dorsomedial hypothalamus nucleus revisited: 1986 update. Brain Res. Rev. 12: 321–381, 1987.
 23. Bhatnagar, S., and M. F. Dallman. Neuroanatomical basis for facilitation of hypothalamic‐pituitary‐adrenal responses to a novel stressor after chronic stress. Neuroscience 84: 1025–1039, 1998.
 24. Bhatnagar, S., and M. J. Meaney. Hypothalamic‐pituitary‐adrenal function in chronic intermittently cold‐stressed neonatally handled and non handled rats. J. Neuroendocrinol. 7: 97–108, 1995.
 25. Bhatnagar, S., J. B. Mitchell, K. Betito, P. Boksa, and M. J. Meaney. Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning. Physiol. Behav. 57: 633–639, 1995.
 26. Biller, B.M.K., H. J. Federoff, J. I. Koenig, and A. Klibanski. Abnormal cortisol secretion and responses to corticotropin‐releasing hormone in women with hypothalmaic amenorrhea. J. Clin. Endocrinol. Metab. 70: 311–317, 1990.
 27. Bjorntorp, P. Adipose tissue distribution and function. Int. J. Obes. 15: 67–81, 1991.
 28. Bjorntorp, P. The regulation of adipose tissue distribution in humans. Int. J. Obes. 20: 291–302, 1996.
 29. Bligh‐Tynan, M. E., S. A. Bhagwat, and T. W. Castonguay. The effects of chronic cold exposure on diurnal corticosterone and aldosterone rhythms in Sprague‐Dawley rats. Physiol. Behav. 54: 363–367, 1993.
 30. Bolinder, J., L. Kager, L. Ostman, and P. Arner. Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis. Diabetes 32: 117–123, 1983.
 31. Borg, M. A., R. S. Sherwin, W. P. Borg, W. V. Tamborlane, and G. I. Shulman. Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hyperglycemia in awake rats. J. Clin. Invest. 99: 361–365, 1997.
 32. Borg, W. P., M. J. During, R. S. Sherwin, M. A. Borg, M. L. Brines, and G. I. Shulman. Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia. J. Clin. Invest. 93: 1677–1682, 1994.
 33. Boyar, R. M., L. D. Hellman, H. Roffwarg, J. Katz, B. Zumoff, J. O'Connor, H. L. Bradlow and D. K. Fukushima. Cortisol secretion and metabolism in anorexia nervosa. N. Engl. J. Med. 296: 190–193, 1977.
 34. Bradbury, M. J., S. F. Akana, and M. F. Dallman. Roles of type I and II corticosteroid receptors in regulation of basal activity in the hypothalamo‐pituitary‐adrenal axis during the diurnal trough and the peak: evidence for a nonadditive effect of combined receptor occupation. Endocrinology 134: 1286–1296, 1994.
 35. Bradbury, M. J., C. S. Cascio, K. A. Scribner, and M. F. Dallman. Stress‐induced adrenocorticotropin secretion: diurnal responses and decreases during stress in the evening are not dependent on corticosterone. Endocrinology 128: 680–688, 1991.
 36. Bray, G. A. Reciprocal relation between the sympathetic nervous system and food intake. Brain Res. Bull. 27: 517–520, 1991.
 37. Bray, G. A., J. Fisler, and D. A. York. Neuroendocrine control of the development of obesity: understanding gained from studies of experimental animal models. Front. Neuroendocrinol. 11: 128–181, 1990.
 38. Bray, G. A., and D. A. York. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol. Rev. 59: 719–809, 1979.
 39. Brindley, D. J., and Y. Rowland. Possible connections between stress, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clin. Sci. (Colch.) 77: 453–461, 1989.
 40. Brodish, A., and M. Odio. Age‐dependent effects of chronic stress on ACTH and corticosterone responses to an acute novel stress. Neuroendocrinology 49: 496–501, 1989.
 41. Bronnegord, M., P. Stierna, and C. Marcus. Glucocorticoid resistant syndromes—molecular basis and clinical presentations. J. Neuroendocrinol. 8: 405–415, 1996.
 42. Bultman, S., E. Michaud, and R. Woychik. Molecular characterization of the mouse agouti locus. Cell 71: 1195–1204, 1992.
 43. Burden, V. R., B. D. White, R. G. Dean, and R. J. Martin. Activity of the hypothalamo‐pituitary‐adrenal axis is elevated in rats with activity‐based anorexia. J. Nutr. 123: 1217–1225, 1993.
 44. Cann, C. E., M. C. Martin, H. K. Cenant, and R. B. Jaffe. Decreased spinal mineral content in amenorrheic women. JAMA 251: 626–629, 1984.
 45. Cascio, C. S., J. Shinsako, and M. F. Dallman. The suprachiasmatic nuclei stimulate evening ACTH secretion in the rat. Brain Res. 423: 173–179, 1987.
 46. Castonguay, T. W., M. F. Dallman, and J. S. Stern. Some metabolic and behavioral effects of adrenalectomy on Zucker rats. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R923–R933, 1986.
 47. Chapman, A. B., D. M. Knight, B. S. Kiekmann, and G. M. Ringold. Analysis of gene expression during differentiation of adipogeneic cells in culture and hormonal control of the developmental program. J. Biol. Chem. 259: 15548–15555, 1984.
 48. Chappell, P. B., M. A. Smith, C. D. Kilts, G. Bissette, J. Ritchie, C. Anderson, and C. B. Nemeroff. Alterations in corticotropin‐releasing factor‐like immunoreactivity in discrete brain regions after acute and chronic stress. J. Neurosci. 6: 2908–2914, 1986.
 49. Choi, S., and M. F. Dallman. The hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food‐entrained oscillator? J. Neurosci. 18: 3843–3852, 1998.
 50. Choi, S., C. Horsley, S. Aguila, and M. F. Dallman. The hypothalamic ventromedial nuclei couple activity in the hypothalamo‐pituitary‐adrenal axis to the morning fed or fasted state. J. Neurosci. 16: 8170–8180, 1996.
 51. Chowdrey, H. S., D. S. Jessop, H. Patel, and S. L. Lightman. Altered adrenocorticotropin, corticosterone and oxytocin responses to stress during chronic salt load. Neuroendocrinology 54: 635–638, 1991.
 52. Chowdrey, H. S., P. J. Larsen, M. S. Harbuz, D. S. Jessop, G. Aguilera, D.J.A. Eckland, and S. L. Lightman. Evidence for arginine vasopressin as the primary activator of the HPA axis during adjuvant‐induced arthritis. Br. J. Pharmacol. 116: 2417–2424, 1995.
 53. Chrousos, G. P., and P. W. Gold. The concepts of stress and stress system disorders. JAMA 267: 1244–1252, 1992.
 54. Chua, S. C.J., D. W. White, X. S. Wu‐Peng, S.‐M. Liu, N. Okada, E. E. Kershaw, W. K. Chung, L. Power‐Hehoe, M. Chua, L. A. Tartaglia, and R. L. Leibel. Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 45: 1141–1143, 1996.
 55. Constantini, A. W., and M. P. Warren. Physical activity, fitness, and reproductive health in women: clinical observations. In: Physical Activity, Fitness, and Health, edited by C. Bouchard, R. J. Shephard, and T. Stephens. Toronto: Human Kinetics, 1994, p. 955–966.
 56. Cousin, B., L. Casteilla, M. Lafontan, L. Ambid, D. Langlin, M.‐F. Berthault, and L. Penicaud. Local sympathetic denervation of white adipose tissue in rats induces preadipocyte proliferation without noticeable changes in metabolism. Endocrinology 133: 2255–2262, 1993.
 57. Cusin, I., F. Rohner‐Jeanrenaud, J. Terrettaz, and B. Jeanrenaud. Hyperinsulinemia and its impact on obesity and insulin resistance. Int. J. Obes. 16: S1–S11, 1992.
 58. Dallman, M. F. Stress update. Adaptations of the hypothalamic‐pituitary‐adrenal axis to chronic stress. Trends Endocrinol. Metab. 4: 62–69, 1993.
 59. Dallman, M. F. Viewing the ventromedial hypothalamus from the adrenal gland. Am. J. Physiol. 246 (Regulatory Integrative Comp. Physiol. 15): R1–R12, 1984.
 60. Dallman, M. F., S. F. Akana, M. J. Bradbury, A. M. Strack, E. S. Hanson, and K. A. Scribner. Regulation of the hypothalamo‐pituitary‐adrenal axis during stress: feedback, facilitation and feeding. Semin. Neurosci. 6: 205–213, 1994.
 61. Dallman, M. F., S. F. Akana, C. S. Cascio, D. N. Darlington, L. Jacobson, and N. Levin. Regulation of ACTH secretion: variations on a theme of B. In: Recent Progress in Hormone Research, edited by J. H. Clark. Orlando, FL: Academic, 1987, p. 113–173.
 62. Dallman, M. F., S. F. Akana, N. Levin, L. Jacobson, C. S. Cascio, D. N. Darlington, S. Suemaru, and K. Scribner. Corticosterone (B) replacement in adrenalectomized rats: insights into the regulation of ACTH secretion. In: The Control of the Hypothalamic‐Pituitary‐Adrenocortical Axis, edited by F. C. Rose. London: International Universities Press, 1989, p. 95–116.
 63. Dallman, M. F., S. F. Akana, K. A. Scribner, M. J. Bradbury, C.‐D. Walker, A. M. Strack, and C. S. Cascio. Stress, feedback and facilitation in the hypothalamo‐pituitary‐adrenal axis. J. Neuroendocrinol. 4: 517–526, 1992.
 64. Dallman, M. F., and M. T. Jones. Corticosteroid feedback control of ACTH secretion on subsequent stress responses in the rat. Endocrinology 92: 1367–1375, 1973.
 65. Dallman, M. F., G. B. Makara, J. L. Roberts, N. Levin, and M. Blum. Corticotrope response to removal of releasing factors and corticosteroids in vivo. Endocrinology 117: 2190–2197, 1985.
 66. Dallman, M. F., A. M. Strack, S. F. Akana, M. J. Bradbury, E. S. Hanson, K. A. Scribner, and M. Smith. Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front. Neuroendocrinol. 14: 303–347, 1993.
 67. Daly, P., and L. Landsberg. Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. Diabetes Care 14: 240–248, 1991.
 68. Daniels‐Severs, A., A. Goodwin, L. C. Keil, and J. Vernikos‐Danellis. Effect of chronic crowding and cold on the pituitary‐adrenal system: responsiveness to an acute stimulus during chronic stress. Pharmacology 9: 348–356, 1973.
 69. de Goeij, D.C.E., R. Binnekade, and F.J.H. Tilders. Chronic stress enhances vasopressin but not corticotropin releasing factor secretion during hypoglycemia. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E394–E399, 1992.
 70. de Goeij, D.C.E., H. Dijkstra, and F.J.H. Tilders. Chronic psychosocial stress enhances vasopressin, but not corticotropin‐releasing factor in the external zone of the median eminence of male rats: relationship to subordinate status. Endocrinology 131: 847–893, 1992.
 71. de Goeij, D.C.E., D. Jezova, and F.J.H. Tilders. Repeated stress enhances vasopressin synthesis in corticotropin releasing factor neurons in the paraventricular nucleus. Brain Res. 577: 165–168, 1992.
 72. de Goeij, D.C.E., R. Kvetnansky, M. H. Whitnall, D. Jezova, F. Berkenbosch, and F.J.H. Tilders. Repeated stress‐induced activation of corticotropin‐releasing factor neurons enhances vasopressin stores and colocalization with corticotropin‐releasing factor in the median eminence. Neuroendocrinology 53: 150–159, 1991.
 73. De Souza, M. J., M. S. Maguire, C. M. Maresh, W. J. Kraemer, K. R. Rubin, and A. B. Loucks. Adrenal activation and the prolactin response to exercise in eumenorrheic and amenorrheic runners. J. Appl. Physiol.: Respir. Environ. Exerc. Physiol. 70: 2378–2387, 1991.
 74. Ding, J.‐H., C. B. Sheckter, B. L. Drinkwater, M. R. Soules, and W. J. Bremner. High serum cortisol levels in exercise‐associated amenorrhea. Ann. Intern. Med. 108: 530–534, 1988.
 75. Dobrakova, M., and J. Jurcovicova. Corticosterone and prolactin responses to repeated handling and transfer of male rats. Exp. Clin. Endocrinol. 83: 21–27, 1984.
 76. Dobrakova, M., and R. Kvetnansky. Specificity of the effect of repeated handling on sympathetic‐adrenomedullary and pituitary‐adrenocortical activity in rats. Psychoneuroendocrinology 18: 163–174, 1993.
 77. Dohanics, J., K.K.J. G. Folly, and G. B. Makara. Long‐term salt loading impairs pituitary responsiveness to ACTH secretogogues and stress in rats. Peptides 11: 59–63, 1990.
 78. Dubuc, P. U. Interactions between insulin and glucocorticoids in the maintenance of genetic obesity. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E550–E555, 1992.
 79. Dunn, A. J., and C. W. Berridge. Physiological and behavioral responses to corticotropin‐releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res. Rev. 15: 71–100, 1990.
 80. Erickson, J. C., G. Hollopeter, and R. D. Palmiter. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274: 1704–1707, 1996.
 81. Feibel, J. H., P. M. Hardy, R. G. Campbell, M. N. Goldstein, and R. J. Joynt. Prognostic value of the stress response following stroke. JAMA 238: 1374–1376, 1977.
 82. Feldman, D. Glucocorticoid receptors and regulation of phosphoenol pyruvate carboxykinase activity in rat kidney and adipose tissue. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E147–E151, 1977.
 83. Feldman, D., and M. Hirst. Glucocorticoids and regulation of phosphoenolpyruvate carboxykinase activity in rat brown adipose tissue. Am. J. Physiol. 235 (Endocrinol. Metab. Gastrointest. Physiol. 4): E197–E202, 1978.
 84. Finlay, J. M., M. J. Zigmond, and E. D. Abercrombie. Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam. Neuroscience 64: 619–628, 1995.
 85. Frederich, R., B. Lollmann, A. Hamann, A. Napolitano‐Rosen, B. B. Kahn, B. B. Lowell, and J. S. Flier. Expression of ob mRNA and its encoded protein in rodents: impact of nutrition and obesity. J. Clin. Invest. 96: 1658–1663, 1995.
 86. Freedman, M. K., B. A. Horwitz, and J. S. Stern. Effect of adrenalectomy and glucocorticoid replacement on the development of obesity. Am. J. Physiol. 250 (Regulatory Integrative Comp. Physiol. 19): R595–R607, 1986.
 87. deleted.
 88. Fried, S. K., C. D. Russell, N. L. Grauso, and R. E. Brolin. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J. Clin. Invest. 92: 2191–2198, 1993.
 89. Friedman, J. M. The alphabet of weight control. Nature 385: 119–120, 1997.
 90. Friedrich, R. C., A. Hamman, S. Anderson, B. Lollmann, B. B. Lowell, and J. S. Flier. Leptin levels reflect body lipid content in mice: evidence for diet‐induced resistance to leptin action. Nat. Med. 1: 1311–1314, 1995.
 91. Fukuhara, K., R. Kvetnansky, G. Cizza, K. Pacak, H. Ohara, D. S. Goldstein, and I. J. Kopin. Interrelations between sympathoadrenal system and hypothalamo‐pituitary‐adrenocortical/thyroid systems in rats exposed to cold stress. J. Neuroendocrinol. 8: 533–541, 1996.
 92. Fukushima, M., K. Tokunaga, J. Lupien, J. W. Kemnitz, and G. A. Bray. Dynamic and static phases of obesity following lesions in PVN and VMH. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 22): R523–R529, 1987.
 93. Garfinkel, P. E., G. M. Brown, H. C. Stanser, and H. Moldofsky. Hypothalamic‐pituitary function in anorexia nervosa. Arch. Gen. Psychiatry 32: 739–744, 1975.
 94. Ghizzoni, L., M. Vanelli, R. Virdis, A. Alberini, C. Volta, and S. Bernasconi. Adrenal steroid and adrenocorticotropin responses to human corticotropin‐releasing hormone stimulation test in adolescents with type I diabetes mellitus. Metabolism 42: 1141–1145, 1993.
 95. Giralt, M., C. Garcia‐Marquez, and A. Armario. Previous chronic ACTH administration does not protect against the effects of acute or chronic stress in male rats. Physiol. Behav. 40: 165–170, 1987.
 96. Glaum, S. R., M. Hara, V. P. Bindokos, C. C. Lee, P. S. Polonsky, G. I. Bell, and R. J. Miller. Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus. Mol. Pharmacol. 50: 230–5, 1996.
 97. Gold, P. W., H. E. Gwittsman, P. C. Aveignie, L. K. Nieman, W. T. Galluci, W. H. Kaye, D. Jimerson, M. Ebert, R. Rittmaster, D. L. Loriaux, and G. P. Chrousos. Abnormal hypothalamic‐pituitary‐adrenal function in anorexia nervosa: pathophysiologic mechanisms in underweight and weight corrected patients. N. Engl. J. Med. 314: 1335–1342, 1986.
 98. Goldstein, L. E., A. M. Rasmussen, B. S. Bunney, and R. H. Roth. Role of the amygdala in the coordination of behavioral, neuroendocrine and prefrontal coartical monoamine responses to psychological stress in the rat. J. Neurosci. 16: 4787–4798, 1996.
 99. Grasso, P., M. C. Leinung, S. P. Ingher, and D. W. Lee. In vivo effects of leptin‐related synthetic peptides on body weight and food intake in female ob/ob mice: localization of leptin activity to domains between amino acid residues 106–140. Endocrinology 138: 1413–1417, 1997.
 100. Gray, G. D., A. M. Bergfors, R. Levin, and S. Levine. Comparison of the effects of restricted morning or evening water intake on adrenocortical activity in female rats. Neuroendocrinology 25: 236–246, 1978.
 101. Gregoire, F. M., P. R. Johnson, and M.R.C. Greenwood. Comparison of the adipoconversion of preadipocytes derived from lean and obese Zucker rats in serum free cultures. Int. J. Obes. 19: 664–670, 1995.
 102. Hanson, E. S., S. F. Akana, A. M. Strack, C. J. Horsley, P. Santana, and M. F. Dallman. Food intake after an overnight fast is not affected by acute alterations in corticosterone but is decreased by chronic adrenalectomy. Stress 1: 83–93, 1996.
 103. Hanson, E. S., M. J. Bradbury, S. F. Akana, K. S. Scribner, A. M. Strack, and M. F. Dallman. The diurnal rhythm in adrenocorticotropin responses to restraint in adrenalectomized rats is determined by caloric intake. Endocrinology 134: 2214–2220, 1994.
 104. Harbuz, M. S., A. J. Chover‐Gonzalez, S. Biwas, and S. L. Lightman. Role of central catecholamines in the modulation of corticotrophin‐releasing factor mRNA during adjuvant‐induced arthritis in the rat. Br. J. Rheumatol. 33: 205–209, 1994.
 105. Harbuz, M. S., D. S. Jessop, S. L. Lightman, and H. S. Chowdrey. The effects of hypertonic saline stress on corticotrophin‐releasing factor, arginine vasopressin, and proenkephalin A mRNAs in the CFY, Sprague‐Dawley and Wistar strains of rat. Brain Res. 667: 6–12, 1994.
 106. Harbuz, M. S., S. A. Nicholson, B. Gillham, and S. L. Lightman. Stress‐responsiveness of hypothalamic corticotrophin‐releasing factor and pituitary proopiomelanocortin mRNAs following high‐dose glucocorticoid treatment and withdrawal in the rat. J. Endocrinol. 127: 407–415, 1990.
 107. Harbuz, M. S., Z. Perveen‐Gill, M. D. Lalies, D. S. Jessup, S. L. Lightman, and H. S. Chowdrey. The role of endogenous serotonin in adjuvant‐induced arthritis in the rat. Br. J. Rheumatol. 35: 112–116, 1996.
 108. Harbuz, M. S., R. G. Rees, D. Eckland, D. S. Jessop, D. Brewerton, and S. L. Lightman. Paradoxical responses of hypothalamic corticotropin‐releasing factor (CRF) messenger RNA (mRNA) and CRF‐41 peptide and adenohypophysial proopiomelanocortin mRNA during chronic inflammatory stress. Endocrinology 130: 1394–1400, 1992.
 109. Harbuz, M. S., R. G. Rees, and S. L. Lightman. HPA axis responses to acute stress and adrenalectomy during adjuvant‐induced arthritis in the rat. Am. J. Physiol. 264 (Regulatory Integrative Comp. Physiol. 33): R179–R185, 1993.
 110. Hauger, R. L., M. Lorang, M. Irwin, and G. Aguilera. CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress. Brain Res. 532: 34–40, 1990.
 111. Hauner, H., P. Schmid, and E. F. Pfeiffer. Glucocorticoids and insulin promote the differentiation of human adipocyte precursor cells into fat cells. J. Clin. Endocrinol. Metab. 64: 832–835, 1987.
 112. Henry, J. P., Neuroendocrine patterns of emotional response. In: Emotion: Theory, Research and Experience, edited by R. Plutchik and H. Kellerman. New York: Academic, 1986, p. 37–60.
 113. Herman, J. P. In situ hybridization analysis of vasopressin gene transcription in the paraventricular and supraoptic nuclei of the rat: regulation by stress and glucocorticoids. J. Comp. Neurol. 363: 15–27, 1995.
 114. Himms‐Hagen, J., Brown adipose tissue thermogenesis: role in thermoregulation, energy regulation and obesity. In: Thermoregulation: Physiology and Biochemistry, edited by E. Schonbaum and P. Lomax. New York: Pergamon, 1990, p. 327–414.
 115. Hobbs, W. L., and C. A. Johnson. Anorexia nervosa: an overview. Am. Fam. Physician 54: 1273–1279, 1996.
 116. Hollingsworth, D. R. Alterations of maternal metabolism in normal and diabetic pregnancies. Differences in insulin dependent, non‐insulin dependent and diabetic pregnancies. Am. J. Obstet. Gynecol. 146: 417–428, 1983.
 117. Honma, K.‐I., S. Honma, and T. Hiroshige. Critical role of food amount for prefeeding corticosterone peak in rats. Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 14): R339–R344, 1983.
 118. Hosker, J. P., M. A. Burnett, D. R. Matthews, and R. C. Turner. Prednisolone enhances B‐cell function independently of ambient glycemic levels in type II diabetes. Metabolism 42: 1116–1120, 1993.
 119. Houssay, B. A. Carbohydrate metabolism. N. Engl. J. Med. 214: 971–986, 1936.
 120. Houssay, B. A., and A. Biasotti. The hypophysis, carbohydrate metabolism and diabetes. Endocrinology 15: 511–523, 1931.
 121. Huszar, D., C. A. Lynch, V. Fairchild‐Huntress, J. H. Dunmora, Q. Fang, L. R. Berkemeier, W. Gu, R. A. Kesterson, B. A. Boston, R. D. Cone, F. J. Smith, L. A. Campfield, P. Burn, and F. Lee. Targeted disruption of the melanocortin‐4 receptor results in obesity in mice. Cell 88: 131–141, 1997.
 122. Imaki, T., J. L. Nahan, C. Rivier, P. E. Sawchenko, and W. W. Vale. Differential regulation of corticotropin‐releasing factor mRNA in rat brain regions by glucocorticoids and stress. J. Neurosci. 11: 585–599, 1991.
 123. Ishikawa, M., S. Ohdo, H. Watanabe, C. Hara, and N. Ogawa. Alterations in circadian rhythm of plasma corticosterone following sociopsychological stress induced by communication box. Physiol. Behav. 57: 41–47, 1995.
 124. Jacobson, L., S. F. Akana, C. S. Cascio, K. Scribner, J. Shinsako, and M. F. Dallman. The adrenocortical system responds slowly to the removal of corticosterone in the absence of stress. Endocrinology 124: 2144–2152, 1989.
 125. Jacobson, L., S. F. Akana, C. S. Cascio, J. Shinsako, and M. F. Dallman. Circadian variations in plasma corticosterone permit normal termination of ACTH responses to stress. Endocrinology 122: 1343–1348, 1988.
 126. Jacobson, L., and R. Sapolsky. Augmented ACTH responses to stress in adrenalectomized rats replaced with constant physiological levels of corticosterone are partially normalized by acute increases in corticosterone. Neuroendocrinology 58: 420–429, 1993.
 127. Jensen, K. H., L. J. Pedersen, E. K. Nielsen, K. E. Heller, J. Ladewig, and E. Jorgensen. Intermittent stress in pigs: effects on behavior, pituitary‐adrenal axis, growth and gastric ulceration. Physiol. Behav. 59: 741–748, 1996.
 128. Jessop, D. S., H. S. Chowdrey, and S. L. Lightman. Inhibition of rat corticotropin‐releasing factor and adrenocorticotropin secretion by an osmotic stimulus. Brain Res. 523: 1–4, 1990.
 129. Kalin, N. H., L. K. Takahashi, and F. L. Chen. Restraint stress increases corticotropin‐releasing factor mRNA content in the amygdala and paraventricular nucleus. Brain Res. 656: 182–186, 1994.
 130. Keller‐Wood, M. E., and M. F. Dallman. Corticosteroid inhibition of ACTH secretion. Endocr. Rev 5: 1–24, 1984.
 131. Kirschbaum, C., E. Gonzalez Bono, N. Hohleder, C. Gessner, K. M. Pirke, A. Salvador, and D. H. Hellhammer. Effects of fasting and glucose load on free cortisol responses to stress and nicotine. J. Clin. Endocrinol. Metab. 82: 1101–1105, 1997.
 132. Kiss, A., and G. Aguilera. Regulation of the hypothalamic pituitary adrenal axis during chronic stress: responses to repeated intraperitoneal hypertonic saline injection. Brain Res. 630: 262–270, 1993.
 133. Kissebah, A. H. Insulin resistance in visceral obesity. Int. J. Obes. 15: 109–115, 1991.
 134. Kissebah, A. H., and A. N. Peiris. Biology of regional body fat distribution. Relationship to non‐insulin‐dependent diabetes. Diabetes Metab. Rev. 4: 615–622, 1989.
 135. Kleyn, P. W., W. Fan, S. G. Kovats, J. J. Lee, J. C. Pulido, Y. Wu, L. R. Berkemeir, D. J. Misumi, L. Holmgren, O. Charlat, E. A. Woolf, O. Tayber, T. Brody, P. Shu, F. Hawkins, B. Kennedy, L. Baldini, C. Ebeling, G. D. Alperin, J. Deeds, N. D. Lakey, J. Culpepper, H. Chen, A. Glucksmann‐Kuis, G. A. Carlson, G. M. Duyk, and J. J. Moore. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell 85: 281–290, 1996.
 136. Kling, M. A., M. A. Demitrack, H. J. J. Whitfield, K. T. Kalogeros, S. J. Listwack, M. D. DeBellis, G. P. Chrousos, P. W. Gold, and H. A. Brandt. Effects of the glucocorticoid antagonist RU 486 on pituitary‐adrenal function in patients with anorexia nervosa and healthy volunteers: enhancement of plasma ACTH and cortisol secretion in underweight patients. Neuroendocrinology 57: 1082–1091, 1993.
 137. Kovacs, K., J. Z. Kiss, and G. B. Makara. Glucocorticoid implants around the hypothalamic paraventricular nucleus prevent the increase of corticotropin‐releasing factor and arginine vasopressin caused by adrenalectomy. Neuroendocrinology 44: 229–234, 1986.
 138. Kovacs, K., and G. B. Makara. Corticosterone and dexamethasone act at different brain sites to inhibit adrenalectomy‐induced adrenocorticotropin secretion. Brain Res. 474: 205–210, 1988.
 139. Kovacs, K. J., and E. Mezey. Dexamethasone inhibits corticotropin‐releasing factor gene expression in the rat paraventricular nucleus. Neuroendocrinology 46: 365–368, 1987.
 140. Kovacs, K. J., and P. E. Sawchenko. Mediation of osmoregulation influences on neuroendocrine corticotropin‐releasing factor expression by the ventral lamina terminalis. Proc. Natl. Acad. Sci. U.S.A. 90: 7681–7685, 1993.
 141. Kovacs, K. J., and P. E. Sawchenko. Sequence of stress‐induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons. J. Neurosci. 16: 262–273, 1996.
 142. Krahn, D. D., B. A. Gosnell, M. Grace, and A. S. Levine. CRF antagonist partially reverses CRF‐ and stress‐induced behavioral effects. Brain Res. Bull. 17: 285–289, 1986.
 143. Krahn, D. D., B. A. Gosnell, and M. J. Majchrzak. The anorectic effects of CRH and restraint stress decrease with repeated exposures. Biol. Psychiatry 27: 1094–1102, 1990.
 144. Krieger, D. T. Food and water restriction shifts corticosterone, temperature, activity and brain amine periodicity. Endocrinology 95: 1195–1201, 1974.
 145. Krieger, D. T. Ventromedial hypothalamic lesions abolish food‐shifted circadian adrenal and temperature rhythmicity. Endocrinology 106: 649–654, 1980.
 146. Krieger, D. T., H. Hauser, and L. C. Krey. Suprachiasmatic nuclear lesions do not abolish food‐shifted circadian adrenal and temperature rhythmicity. Science 197: 398–399, 1977.
 147. Krowzowski, Z. S., and J. W. Funder. Renal mineralocorticoid receptors and hippocampal corticosterone binding species have identical intrinsic steroid specificity. Proc. Natl. Acad. Sci. U.S.A. 80: 6056–6060, 1983.
 148. Bernardis, L. L., and L. L. Bellinger. Further nutritional characterization of dorsomedial hypothalamic hypophagia in rats: diet consistency, finickiness, self‐selection of diets, starvation and realimentation and “stress eating”. J. Nutr. 111: 721–732, 1981.
 149. Lachuer, J., I. Delton, M. Buda, and M. Tappaz. The habituation of brainstem catecholaminergic cell groups to chronic daily stress is stress specific like that of the hypothalamo‐pituitary‐adrenal axis. Brain Res. 638: 196–202, 1994.
 150. Larsen, P. J., D. S. Jessop, H. S. Chowdrey, S. L. Lightman, and J. D. Mikkelsen. Chronic administration of glucocorticoids directly upregulates prepro‐neuropeptide Y and Y1‐receptor mRNA levels in the arcuate nucleus of the rat. J. Neuroendocrinol. 6: 153–159, 1994.
 151. Larue‐Achagiotis, C., and J. Le Magnen. Effects of a daytime infusion of exogenous insulin on subsequent nocturnal food intake and body weight in rats. Physiol. Behav. 30: 573–576, 1983.
 152. Laughlin, G. A., and S.S.C. Yen. Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J. Clin. Endocrinol. Metabol. 82: 318–321, 1997.
 153. Lee, G. H., R. Proenca, J. M. Montaz, K. M. Carroll, J. G. Darviszadeh, J. I. Lee, and J. M. Friedman. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379: 632–635, 1996.
 154. Leedom, L. J., and W. P. Meeham. The psychoneuroendocrinology of diabetes mellitus in rodents. Psychoneuroendocrinology 14: 275–294, 1989.
 155. Leibel, R. L., N. K. Edens, and S. K. Fried. Physiologic basis for control of body fat distribution in humans. Annu. Rev. Nutr. 9: 417–443, 1989.
 156. Leibowitz, S. F. Neruochemical‐neuroendocrine systems in the brain controlling macronutrient intake and metabolism. Trends Neurosci. 15: 491–497, 1992.
 157. Le Magnen, J. Neurobiology of Feeding and Nutrition. San Diego: Academic, 1992.
 158. Lemaire, V., and P. Mormede. Telemetered recording of blood pressure and heart rate in different strains of rats during chronic social stress. Physiol. Behav. 58: 1181–1188, 1995.
 159. Levin, B. E. Neurological Regulation of Body Weight. Boca‐Raton, FL: CRC, 1987.
 160. Lightman, S. L., and M. S. Harbuz. Expression of corticotropin‐releasing factor mRNA in response to stress. Ciba Found. Symp. 172: 173–186, 1993.
 161. Lindvall, A., A. Bjorkland, A. Nobin, and U. Stenevi. The adrenergic innervation of the rat thalamus as revealed by the glycoxylic acid fluorescence method. J. Comp. Neurol. 154: 317–348, 1974.
 162. Linkowski, P., J. Meldelwicz, R. Leclercq, M. Brasseur, P. Hubain, J. Golstein, G. Copinschi, and E. Van Cauter. The 24‐hour profile of adrenocorticotropin and cortisol in major depressive illness. J. Clin. Endocrinol. Metab. 61: 429–438, 1985.
 163. Long, C.N.H. The adrenal cortex and carbohydrate metabolism. Endocrinology 26: 309–344, 1940.
 164. Long, C.N.H. A discussion of the mechanism of action of adrenal cortical hormones on carbohydrate and protein metabolism. Endocrinology 30: 870–883, 1942.
 165. Loucks, A. B., Physical activity, fitness and female reproductive morbidity. In: Physical Activity, Fitness, and Health, edited by C. Bouchard, R. J. Shephard, and T. Stephens. Toronto: Human Kinetics, 1994, p. 943–954.
 166. Loucks, A. B., and S. M. Horvath. Exercise‐induced stress responses of amenorrheic and eumenorrheic runners. J. Clin. Endocrinol. Metab. 59: 1109–1120, 1984.
 167. Loucks, A. B., K. A. Laughlin, J. F. Mortola, L. Girton, J. C. Nelson, and S.C.C. Yen. Hypothalamic‐pituitary‐thyroidal function in eumenorrheic and amenorrheic athletes. J. Clin. Endocrinol. Metab. 75: 514–518, 1992.
 168. Lu, D., D. Willard, I. R. Patel, S. Kadwell, L. Overton, T. Kost, M. Luther, W. Chen, R. P. Waychik, W. K. Wilkison, and R. D. Cone. Agouti protein is an antagonist of the melanocyte‐stimulating‐hormone receptor. Nature 371: 799–802, 1994.
 169. Luiten, P.G.M., G. J. ter Horst, and A. B. Steffens. The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism. Prog. Neurobiol. 28: 1–54, 1987.
 170. Maffei, M. S., M. M. Barone, B. Moon, M. Dammerman, E. Ravussin, C. Bogardus, D. S. Ludwig, J. S. Flier, M. Talley, S. Auerbach, and J. M. Friedman. Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes 45: 679–682, 1996.
 171. Makino, S., P. W. Gold, and J. Schulkin. Corticosterone effects on corticotropin‐releasing hormone mRNA in the central nucleus of the amygdala and the parvocellular region of the paraventricular nucleus of the hypothalamus. Brain Res. 640: 105–112, 1994.
 172. Mantzoros, C. S., D. Qu, R. C. Frederich, V. S. Susulic, B. B. Lowell, E. Maratos‐Flier, and J. S. Flier. Activation of β3 adrenergic receptors suppresses leptin expression and mediates a leptin‐independent inhibition of food intake in mice. Diabetes 45: 909–914, 1996.
 173. Marcus, R., C. Cann, P. Madvig, J. Minkoff, M. Goddard, M. Bayer, M. Martin, L. Guadiani, W. Haskell, and H. Genant. Menstrual function and bone mass in elite women distance runner. Ann. Intern. Med. 102: 158–162, 1985.
 174. Marti, O., A. Gavalda, T. Jolin, and A. Armario. Effect of regularity of exposure to chronic immobilization stress on the circadian pattern of pituitary adrenal hormones, growth hormone and thyroid stimulating hormone in the adult male rat. Psychoneuroendocrinology 18: 67–77, 1993.
 175. Marti, O., J. Marti, and A. Armario. Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure. Physiol. Behav. 55: 747–755, 1994.
 176. Mayo‐Smith, W., C. W. Hayes, M. K. Biller, A. Klibanski, H. Rosenthal, and D. I. Rosenthal. Body fat distribution measured with CT: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing's syndrome. Radiology 170: 515–518, 1989.
 177. McKittrick, C. R., D. C. Blanchard, R. J. Blanchard, B. S. McEwen, and R. R. Sakai. Serotonin receptor binding in a colony model of chronic social stress. Biol. Psychiatry 37: 383–393, 1995.
 178. Mercer, J. G., N. Hoggard, L. M. Williams, C. B. Lawrence, L. T. Hannah, P. J. Morgan, and P. Trayhurn. Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus. J. Neuroendocrinol. 8: 733–735, 1996.
 179. Miller, A. H., R. L. Spencer, A. Husain, R. Rhee, B. S. McEwen, and M. Stein. Differential expression of type I adrenal steroid receptors in immune tissue is associated with tissue‐specific regulation of type II receptors by aldosterone. Endocrinology 133: 2133–2140, 1993.
 180. Miller, W. L., and J. B. Tyrrell. Endocrinology and Metabolism. New York: McGraw‐Hill, 1995.
 181. Mistlberger, R. E. Circadian food‐anticipatory activity: formal models and physiological mechanisms. Neurosci. Biobehav. Rev. 18: 171–195, 1994.
 182. Moga, M. M., R. P. Weis, and R. Y. Moore. Efferent projections of the paraventricular thalamic nucleus of the rat. J. Comp. Neurol. 359: 221–238, 1995.
 183. Moore, R. Y., and V. B. Eichler. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res. 42: 201–206, 1972.
 184. Morley, J. E. Neuroendocrine regulation of appetite and weight. Endocr. Rev. 8: 256–287, 1987.
 185. Morley, J. E., and A. S. Levine. Corticotropin‐releasing factor, grooming and ingestive behaviors. Life Sci. 31: 1459–1464, 1982.
 186. Mormede, P., V. Lemaire, N. Castanon, J. Dulluc, M. Laval, and M. Le Moal. Multiple neuroendocrine responses to chronic social stress: interaction between individual characteristics and situational factors. Physiol. Behav. 47: 1099–1105, 1990.
 187. Munk, M.H.J., P. R. Roelfsema, P. Konig, A. K. Engel, and W. Singer. Role of reticular activation in the modulation of intra‐cortical synchronization. Science 272: 271–274, 1996.
 188. Murakami, K., S. F. Akana, and M. F. Dallman. Corticosteroid feedback inhibition of dopamine‐B‐hydroxylase, and facilitation of acute stress responses. J. Neuroendocrinol. 9: 601–608, 1997.
 189. Nagai, K., and H. Nakagawa. Central Regulation of Energy Metabolism with Special Reference to Circadian Rhythm. Boca Raton, FL: CRC, 1992.
 190. Nicholson, S. A., E. A. Campbell, B. Gillham, and M. T. Jones. Recovery of the components of the hypothalamo‐pituitary‐adrenocortical axis in the rat after chronic treatment with prednisolone. J. Endocrinol. 113: 239–247, 1987.
 191. Nicholson, S. A., B. Gillham, and M. T. Jones. Influence of prolonged glucocorticoid treatment on intracellular mechanisms involved in ACTH secretion in the rat. J. Mol. Endocrinol. 1: 202–212, 1988.
 192. Nissenbaum, L. K., and E. D. Abercrombie. Enhanced tyrosine hydroxylation in hippocampus of chronically stressed rats upon exposure to a novel stressor. J. Neurochem. 58: 276–281, 1992.
 193. Nissenbaum, L. K., M. J. Zigmond, A. Sved, and E. D. Abercrombie. Prior exposure to chronic stress results in enhanced synthesis and release of hippocampal norepinephrine in response to a novel stress. J. Neurosci. 11: 1478–1484, 1991.
 194. Noben‐Trauth, K., J. K. Naggert, M. A. North, and P. M. Nishina. A candidate gene for the mouse mutation tubby. Nature 380: 534–538, 1996.
 195. Nolten, W. E., M. D. Lindheimer, P. A. Rueckert, S. Oparil, and E. N. Ehrlich. Diurnal patterns and regulation of cortisol secretion in pregnancy. J. Clin. Endocrinol Metab. 51: 466–472, 1980.
 196. Odio, M., and A. Brodish. Age‐related adaptation of pituitary‐adrenocortical responses to stress. Neuroendocrinology 49: 382–388, 1989.
 197. Odio, M. R., and A. Brodish. Effects of chronic stress on in vivo pituitary‐adrenocortical responses to corticotropin releasing hormone. Neuropeptides 15: 143–152, 1990.
 198. Oka, M. Effect of cerebrovascular accident on the level of 17‐hydroxycorticosteroids in plasma. Acta Med. Scand. 154: 221–226, 1956.
 199. Olsson, T., M. Astrom, S. Eriksson, and A. Forssel. Hypercortisolism revealed by the dexamethasone suppression test with acute ischemic stroke. Stroke 20: 1690–1695, 1989.
 200. Oomura, Y., and H. Yoshimatsu. Neural network of glucose monitoring system. J. Auton. Nerv. Syst. 10: 359–372, 1984.
 201. Ostman‐Smith, I. Adaptive changes in the sympathetic nervous system and some effector organs of the rat following long term exercise or cold acclimation and the role of cardiac sympathetic nerves in the genesis of cardiac hypertrophy. Acta Physiol. Scand. S477: 1–102, 1979.
 202. Ottenweller, J. E., B. H. Natelson, D. L. Pitman, and S. D. Drastal. Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress‐related mental illness. Biol. Psychiatry 26: 829–841, 1989.
 203. Owens, M. J., and C. B. Nemeroff. Physiology and pharmacology of corticotropin‐releasing factor. Pharmacol. Rev. 43: 425–473, 1991.
 204. Pacak, K., M. Palkovits, I. J. Kopin, and D. S. Goldstein. Stress‐induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary‐adrenocortical and sympathoadrenal activity: in vivo microdialysis studies. Front. Neuroendocrinol. 16: 89–150, 1995.
 205. Parkes, D., K. Rivest, S. Lee, C. Rivier, and W. Vale. Corticotropin‐releasing factor activates c‐fos, NGFI‐B and CRF gene expression within the paraventricular nucleus of the rat hypothalamus. Mol. Endocrinol. 7: 1357–1367, 1993.
 206. Parkinson, W. L., and H. P. Weingarten. Dissociative analysis of ventromedial hypothalamic obesity syndrome. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 28): R829–R835, 1990.
 207. Pasquali, R., S. Cantobelli, F. Casimirri, M. Capelli, L. Bortoluzzi, R. Flamia, A.M.M. Labate, and L. Barbara. The hypothalamic‐pituitary‐adrenal axis in obese women with different patterns of body fat distribution. J. Clin. Endocrinol. Metab 77: 341–346, 1993.
 208. Pedersen, S. B., J. D. Borglum, T. Moller‐Pedersen, and B. Richelsen. Characterization of nuclear corticosteroid receptors in rat adipocytes. Regional variations and modulatory effects of hormones. Biochem. Biophys. Acta 1134: 303–308, 1992.
 209. Pedersen, S. B., M. Jonler, and B. Richelsen. Characterization of regional and gender differences in glucocorticoid receptors and lipoprotein lipase activity on human adipose tissue. J. Clin. Endocrinol. Metab. 78: 1354–1359, 1994.
 210. Pellymounter, M. A., M. J. Cullen, M. B. Baker, R. Hecht, D. Winters, T. Boone, and F. Collins. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543, 1995.
 211. Peng, Z.‐C., G. Grassi‐Zucconi, and M. Bentivoglio. Fos‐related protein expression in the midline paraventricular nucleus of the rat thalamus: basal oscillation and relationship with limbic efferents. Exp. Brain Res. 104: 21–29, 1995.
 212. Phelps, R. L., B. E. Metzger, and N. Freinkel. Carbohydrate metabolism in pregnancy. XVII Diurnal profiles of plasma glucose, insulin, free fatty acids, triglycerides, cholesterol, and individual amino acids in late pregnancy. Am. J. Obstet. Gynecol. 140: 730–736, 1981.
 213. Pirke, K. M., A. Broocks, T. Wilckens, R. Marquard, and U. Schweiger. Starvation‐induced hyperactivity in the rat: the role of endocrine and neurotransmitter changes. Neurosci. Biobehav. Rev. 17: 287–294, 1993.
 214. Pittman, D. L., J. E. Ottenweller, and B. H. Natelson. Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation. Physiol. Behav. 43: 47–55, 1988.
 215. Plotsky, P. M., Regulation of the adrenocortical axis: hypophysiotropic coding, catecholamines and glucocorticoids. In: The Control of the Hypothalamo‐Pituitary‐Adrenocortical Axis, edited by F. C. Rose: 1989, p. 131–146. Internat. Univ. Press Inc. Madison Co.
 216. Plotsky, P. M., and P. E. Sawchenko. Hypophysial‐portal plasma levels, median eminence content and immunohistochemical staining of corticotropin‐releasing factor, arginine vasopressin and oxytocin after pharmacological adrenalectomy. Endocrinology 120: 1361–1369, 1987.
 217. Powley, T. L., C. A. Opsahl, J. E. Cox, and H. P. Weingarten. The role of hypothalamus in energy balance. In: Handbook of the Hypothalamus, edited by P. J. Morgane and J. Panksepp. New York: Dekker, 1980, p. 211–298.
 218. Quirce, C. M., and R. P. Maickel. Alterations of biochemical parameters by acute and repetitive stress situations in mice. Psychoneuroendocrinology 6: 91–97, 1981.
 219. Ratka, A., W. Sutanto, M. Bloemers, and E. R. de Kloet. On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulations. Neuroendocrinology 50: 117–123, 1989.
 220. Reaven, G. M., H. Lithell, and L. Landsberg. Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathetic nervous system. N. Engl. J. Med. 334: 374–381, 1996.
 221. Rebuffe‐Scrive, M., M. Bronnegard, A. Nilsson, J. Eldh, J.‐A. Gustafsson, and P. Bjorntorp. Steroid hormone receptors in human adipose tissues. J. Clin. Endocrinol. Metab. 71: 1215–1219, 1990.
 222. Rebuffe‐Scrive, M., M. L. Enk, N. Crona, P. Lonnroth, L. Abrahamson, U. Smith, and P. Bjorntorp. Fat cell metabolism in different regions of women. Effect of menstrual cycle, pregnancy and lactation. J. Clin. Invest. 75: 1973–1976, 1985.
 223. Rebuffe‐Scrive, M., M. Krotiewski, J. Elfverson, and P. Bjorntorp. Glucocorticoid hormone binding to human adipose tissue. Eur. J. Clin. Invest. 15: 267–271, 1988.
 224. Rebuffe‐Scrive, M., U. A. Walsh, B. McEwen, and J. Rodin. Effect of chronic stress and exogenous glucocorticoids on regional fat distribution and metabolism. Physiol. Behav. 52: 583–590, 1992.
 225. Reul, J. M. H. M., and E. R. de Kloet. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117: 2505–2511, 1985.
 226. Rohner‐Jeanrenaud, F. A neuroendocrine reappraisal of the dual‐centre hypothesis: its implications for obesity and insulin resistance. Int. J. Obes. 19: 517–534, 1995.
 227. Rohner‐Jeanrenaud, F., and B. Jeanrenaud. Aspects of neuroregulation of body composition and insulin secretion. Int. J. Obes. 15: 117–122, 1991.
 228. Routtenberg, A. Self starvation of rats living in activity wheels: adaptation effects. J. Comp. Psychol. Physiol. 66: 234–238, 1968.
 229. Russell, J. C., R. M. Amy, V. Nanickavel, P. J. Dolphin, W. F. Epling, D. Pierce, and D. P. Boer. Prevention of myocardial disease in JCR:LA‐corpulent rats by running. J. Appl. Physiol.: Repir. Environ. Exerc. Physiol. 66: 1649–1655, 1989.
 230. Saito, M., K. Nishimura, and H. Kato. Modification of circadian cortisol rhythm by cyclic and continuous enteral nutrition. J. Nutr. Sci. Vitaminol. (Tokyo) 35: 639–647, 1989.
 231. Sakellaris, P. C., and J. Vernikos‐Danellis. Increased rate of response of the pituitary‐adrenal system in rats adapted to chronic stress. Endocrinology 97: 597–602, 1975.
 232. Samuels, M. H., and P. A. McDaniel. Thyrotropin levels during hydrocortisone infusion that mimic fasting‐induced cortisol elevations: a clinical research center study. J. Clin. Endocrinol. Metab. 82: 3700–3704, 1997.
 233. Santana, P., S. F. Akana, E. S. Hanson, R. J. Sebastian, and M. F. Dallman. Aldosterone and dexamethasone both stimulate energy acquisition whereas only the glucocorticoid alters energy storage. Endocrinology 136: 2214–2222, 1995.
 234. Sapolsky, R. M., L. C. Krey, and B. S. McEwen. Stress down‐regulates corticosterone receptors in a site‐specific manner in the brain. Endocrinology 114: 287–292, 1984.
 235. Sarlis, N. J., H. S. Chowdrey, A. Stephanou, and S. L. Lightman. Chronic activation of the hypothalamo‐pituitary‐adrenal axis and loss of circadian rhythm during adjuvant‐induced arthritis in the rat. Endocrinology 130: 1775–1779, 1992.
 236. Sawchenko, P. E., C. A. Arias, and M. T. Mortrud. Local tetrodotoxin blocks chronic stress effects on corticotropin‐releasing factor and vasopressin messenger ribonucleic acids in hypophysiotropic neurons. J. Neuroendocrinol. 5: 341–348, 1993.
 237. Schlaghecke, R., E. Kornely, R. T. Santen, and P. Ridderskamp. The effect of long‐term glucocorticoid therapy on pituitary‐adrenal responses to exogenous corticotropin‐releasing hormone. N. Engl. J. Med. 326: 226–230, 1992.
 238. Schulkin, J., B. S. McEwen, and P. W. Gold. Allostasis, amygdala, and anticipatory angst. Neurosci. Biobehav. Rev. 18: 385–396, 1994.
 239. Schwartz, M. W., M. F. Dallman, and S. C. Woods. The hypothalamic response to starvation: implications for the study of wasting disorders. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R949–R957, 1995.
 240. Schwartz, M. W., D. P. Figlewicz, D. G. Baskin, S. C. Woods, and D. J. Porte. Insulin in the brain: a hormonal regulator of energy balance. Endocr. Rev. 13: 387–414, 1992.
 241. Schwartz, M. W., D. P. Figlewicz, D. G. Baskin, S. C. Woods, and D. J. Porte. Update 1994. Insulin and the central control of energy balance. Endocr. Rev. Monogr. 2: 109–113, 1994.
 242. Schwartz, M. W., E. Peskind, M. Raskind, E. J. Boyko, and D. J. Porte. Cerebrospinal fluid leptin levels: relationship to plasma levels and adiposity in humans. Nat. Med. 2: 589–593, 1996.
 243. Scribner, K. A., S. F. Akana, C.‐D. Walker, and M. F. Dallman. Streptozotocin‐diabetic rats exhibit facilitated adrenocorticotropin responses to acute stress, but normal sensitivity to feedback by corticosteroids. Endocrinology 133: 2667–2674, 1993.
 244. Scribner, K. A., C.‐D. Walker, C. S. Cascio, and M. F. Dallman. Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues. Endocrinology 129: 99–108, 1991.
 245. Selye, H. The general adaptation syndrome and the diseases of adaptation. J. Clin. Endocrinol. 6: 117–230, 1946.
 246. Shibasaki, T., N. Yamauchi, Y. Kato, A. Masuda, T. Imaki, M. Hotta, H. Demura, H. Oono, N. Ling, and K. Shizume. Involvement of corticotropin‐releasing factor in restraint stress‐induced anorexia and reversion of the anorexia by somatostatin in the rat. Life Sci. 43: 1103–1110, 1988.
 247. Sjogren, J., M. Weck, A. Nilsson, M. Ottosson, and P. Bjorntorp. Glucocorticoid hormone binding to rat adipocytes. Biochim. Biophys. Acta 1224: 17–21, 1994.
 248. Speake, B. K., S. M. Parkin, and D. S. Robinson. Regulation of the synthesis of lipoprotein lipase in adipose tissue by dexamethasone. Biochim. Biophys. Acta 881: 155–157, 1986.
 249. Spencer, R. L., J. K. Paul, B. A. Kalman, and M. A. Cole. Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor‐dependent regulation of hypothalamic‐pituitary‐adrenal axis activity. Endocrinology 139: 2718–2726, 1998.
 250. Spiegelman, B. M., and J. S. Flier. Adipogenesis and obesity: rounding out the big picture. Cell 87: 377–389, 1996.
 251. Steele, R., Influences of corticosteroids on protein and carbohydrate metabolism. In: Handbook of Physiology Adrenal Gland, edited by H. Blaschko, G. Sayers, and A. D. Smith. Washington, D.C.: Am. Physiol. Soc., 1975, sect. 7, vol. VI, p. 135–168.
 252. Stehling, O., H. Doring, J. Ertl, G. Preibisch, and I. Schmidt. Leptin reduces juvenile fat stores by altering the circadian cycle of energy expenditure. Am. J. Physiol. 271 (Regulatory Integrative Comp. Physiol. 40): R1770–R1774, 1996.
 253. Stephan, F. K., and I. Zucker. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc. Nat. Acad. Sci. U.S.A. 69: 1583–1586, 1972.
 254. Stephens, T. W., M. Basinski, P. K. Briston, J. M. Bue‐Vasseskey, L. G. Burgett, L. Craft, J. Hale, J. Hoffman, H. Hsiung, K. Kriausciunas, W. MacKellar, P.R.J. Roseck, B. Schoner, D. Smith, F. C. Tiley, X. Y. Zhang, and N. Heiman. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377: 530–532, 1995.
 255. Strack, A. M., M. J. Bradbury, and M. F. Dallman. Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R183–R191, 1995.
 256. Strack, A. M., C. J. Horsley, R. J. Sebastian, S. F. Akana, and M. F. Dallman. Glucocorticoids and insulin: complex interaction on brown adipose tissue. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1209–R1216, 1995.
 257. Strack, A. M., R. J. Sebastian, M. W. Schwartz, and M. F. Dallman. Glucocorticoids and insulin: reciprocal signals for energy balance. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R142–R149, 1995.
 258. Strunkard, A. J., M. H. Fernstrom, A. Price, E. Frank, and D. J. Kupfer. Direction of weight change in recurrent depression. Consistency across episodes. Arch. Gen. Psychiatry 47: 857–860, 1990.
 259. Suemaru, S., D. N. Darlington, S. F. Akana, C. S. Cascio, and M. F. Dallman. Ventromedial hypothalamic lesions inhibit corticosteroid feedback regulation of basal ACTH during the trough of the circadian rhythm. Neuroendocrinology 61: 453–463, 1995.
 260. Swanson, L. W., and D. M. Simmons. Differential steroid hormone and neural influences on peptide mRNA levels in CRH cells of the paraventricular nucleus: a hybridization histochemical study in the rat. J. Comp. Neurol. 285: 413–435, 1989.
 261. Tanaka, H., Y. Ueta, U. Yamashita, H. Kannan, and H. Yamashita. Biphasic changes in behavioral, endocrine and sympathetic systems in adjuvant arthritis in Lewis rats. Brain Res. Bull. 39: 33–37, 1996.
 262. Tartaglia, L. A., M. Dembrski, X. Weng, N. Deng, J. Culpepper, R. Devos, G. J. Richards, L. A. Campfield, K. T. Clark, J. Deeds, C. Muir, S. Sanker, A. Moriarty, K. J. Moore, J. S. Smutko, G. G. Mays, E. A. Woolf, C. A. Monroe, and R. I. Tepper. Identification and expression cloning of a leptin receptor, OB‐R. Cell 83: 1263–1271, 1995.
 263. Tempel, D. L., and S. F. Leibowitz. Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism. J. Neuroendocrinol. 6: 479–501, 1994.
 264. Tizabi, Y., and G. Aguilera. Desensitization of the hypothalamic‐pituitary‐adrenal axis following prolonged administration of corticotropin‐releasing hormone or vasopressin. Neuroendocrinology 56: 611–618, 1992.
 265. Tokunaga, K., M. Fukushima, J. R. Lupien, G. A. Bray, J. W. Kemnitz, and R. Schemmel. Effects of food restriction and adrenalectomy in rats with VMN or PVN lesions. Physiol. Behav. 45: 1131–1137, 1987.
 266. Truett, K. E., N. Bahary, J. M. Friedman, and R. L. Leibel. Rat obesity gene (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db). Proc. Nat. Acad. Sci. U.S.A. 88: 7806–7809, 1991.
 267. Turner, B. H., and M. Herkenham. Thalamoamygdaloid projections in the rat: a test of the amygdala's role in sensory processing. J. Comp. Neurol. 313: 295–325, 1991.
 268. van Cauter, E., K. S. Polonsky, J. D. Blackman, R. D. J. Sturis, M. M. Byrne, and A. J. Scheen. Abnormal temporal patterns of glucose tolerance in obesity: relationship to sleep‐related growth hormone secretion and circadian cortisol rhythmicity. J. Clin. Endocrinol. Metab. 79: 1797–1805, 1994.
 269. Vanderweele, D. A., E. Haraczkiewicz, and T. B. Van Itallie. Elevated insulin and satiety in obese and normal weight rats. Appetite 3: 99–109, 1982.
 270. Vernikos, J., M. F. Dallman, C. Bonner, A. Katzen, and J. Shinsako. Pituitary‐adrenal function in rats chronically exposed to cold. Endocrinology 110: 413–420, 1982.
 271. Viau, V., S. Sharma, P. Plotsky, and M. J. Meaney. Increased plasma ACTH responses to stress in nonhandled compared with handled rats require basal levels of corticosterone and are associated with increased levels of ACTH secretogogues in the median eminence. J. Neurosci. 13: 1097–1105, 1993.
 272. Walker, C.‐D., K. A. Scribner, J. S. Stern, and M. F. Dallman. Obese Zucker (fa/fa) rats exhibit normal target sensitivity to corticosterone and increased drive to adrenocorticotropin during the diurnal trough. Endocrinology 131: 2629–2637, 1992.
 273. Warren, M. P., J. Brooks‐Gunn, L. H. Hamilton, L. F. Warren, and W. G. Hamilton. Scoliosis and fractures in young ballet dancers: relation to delayed menarche and secondary amenorrhea. N. Engl. J. Med. 314: 1348–1353, 1986.
 274. Watts, A. G., and G. Sanchez‐Watts. Region specific regulation of neuropeptide mRNA levels in neurones of the limbic forebrain by adrenal steroids. J. Physiol. (Lond.) 484: 721–736, 1995.
 275. Weidenfeld, J., A. P. Corcos, A. Wohlman, and S. Feldman. Characterization of the 2‐deoxyglucose effect on the adrenocortical axis. Endocrinology 134: 1924–1931, 1994.
 276. Whitnall, M. H. Regulation of the hypothalamic corticotropin‐releasing hormone neurosecretory system. Prog. Neurobiol. 40: 573–629, 1993.
 277. Wilkinson, C. W., J. Shinsako, and M. F. Dallman. Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat. Endocrinology 104: 350–359, 1979.
 278. Woodward, C.J.H., and P. W. Emery. Energy balance in rats given chronic hormone treatment 1. Effects of long‐acting insulin. Br. J. Nutr. 61: 437–444, 1989.
 279. Wu, P., and G. V. Childs. Cold and novel environment stress affects AVP mRNA in the paraventricular nucleus, but not the supraoptic nculeus: an in situ hybridization study. Mol. Cell. Neurosci. 1: 233–249, 1990.
 280. Young, E. A., S. F. Akana, and M. F. Dallman. Decreased sensitivity to glucocorticoid fast feedback in chronically stressed rats. Neuroendocrinology 51: 536–542, 1990.
 281. Young, E. A., S. P. Kwak, and J. Kottak. Negative feedback regulation following administration of chronic exogenous corticosterone. J. Neuroendocrinol. 7: 37–45, 1995.
 282. Young, J. B., and L. Landsberg. Suppression of sympathetic nervous system during fasting. Science 196: 1473–1475, 1977.

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Article Title: Chronic Stress and Energy Balance: Role of the Hypothalamo‐Pituitary‐Adrenal Axis
 

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Mary F. Dallman, Seema Bhatnagar. Chronic Stress and Energy Balance: Role of the Hypothalamo‐Pituitary‐Adrenal Axis. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 179-210. First published in print 2001. doi: 10.1002/cphy.cp070410