Comprehensive Physiology Wiley Online Library

Vitamin D Endocrine System and Calcium and Phosphorus Homeostasis

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Physiological Effects of Vitamin D and its Active Metabolites on Calcium and Phosphorus Homeostasis
2 Sources of Vitamin D
3 Transport of Vitamin D and its Metabolites in Plasma
4 Metabolism of Vitamin D3 to 25‐Hydroxyvitamin D3
5 Metabolism of 25‐Hydroxyvitamin D3
6 Regulation of the 25‐Hydroxyvitamin D3–1α‐Hydroxylase Enzyme
6.1 Parathyroid Hormone
6.2 Phosphorus Concentrations
6.3 Calcium: Direct Effects
6.4 1,25‐Dihydroxyvitamin D3
6.5 Calcitonin
6.6 Hydrogen Ion
6.7 Sex Steroids
6.8 Glucocorticoids
6.9 Pituitary Hormones
6.10 Thyroid Hormone
6.11 Pregnancy
7 Catabolism of 1,25‐Dihydroxyvitamin D3
8 Physiological Adaptations that Occur in Response to Changes in Serum Calcium and Phosphate Concentrations
8.1 Hypocalcemia and Hypercalcemia
8.2 Hypophosphatemia and Hyperphosphatemia
9 Pathophysiology and Physiology of the 1,25‐Dihydroxyvitamin D3 System
10 Mechanisms of Action of 1,25‐Dihydroxyvitamin D3
10.1 1,25‐Dihydroxyvitamin D3 in the Intestine
10.2 Processes in the Cell That Are Mediated by 1,25‐Dihydroxyvitamin D3
10.3 Intestinal Brush Border Events Induced by 1,25‐Dihydroxyvitamin D3
10.4 Events at the Contraluminal Border
10.5 Effects of 1,25‐Dihydroxyvitamin D3 on the Intestinal Cell
10.6 1,25‐Dihydroxyvitamin D3 in the Kidney
Figure 1. Figure 1.

Calcium balance in man.

From Nordin 169
Figure 2. Figure 2.

Estimate of vitamin D–dependent and independent calcium absorption in man.

From Shiekh 212
Figure 3. Figure 3.

Phosphorus balance in man.

From Nordin 169
Figure 4. Figure 4.

Generation of vitamin D3 in skin. Movement of vitamin D3 out of skin in association with vitamin D–binding protein is speculative.

Figure 5. Figure 5.

Formation of 25‐hydroxyvitamin D3 in liver microsomes and mitochondria.

Figure 6. Figure 6.

Microsomal vitamin D–25‐hydroxylase enzyme.

From DeLuca 56
Figure 7. Figure 7.

Formation of 1,25‐dihydroxyvitamin D3 and 24R,25‐dihydroxyvitamin D3 from 25‐hydroxyvitamin D3 in renal mitochondria.

Figure 8. Figure 8.

25‐Hydroxyvitamin D3–1α‐hydroxylase system in chick renal mitochondria.

From DeLuca 56
Figure 9. Figure 9.

The metabolism of 1,25‐dihydroxyvitamin D3.

From Kumar 125
Figure 10. Figure 10.

Physiological adaptations to hypo‐ and hypercalcemia. PTH, parathyroid hormone; CT, calcitonin.

Figure 11. Figure 11.

Physiological adaptations to hypo‐ and hyperphosphatemia.

Figure 12. Figure 12.

Thermodynamic considerations in absorption of calcium in intestinal cell.

From Wasserman 245


Figure 1.

Calcium balance in man.

From Nordin 169


Figure 2.

Estimate of vitamin D–dependent and independent calcium absorption in man.

From Shiekh 212


Figure 3.

Phosphorus balance in man.

From Nordin 169


Figure 4.

Generation of vitamin D3 in skin. Movement of vitamin D3 out of skin in association with vitamin D–binding protein is speculative.



Figure 5.

Formation of 25‐hydroxyvitamin D3 in liver microsomes and mitochondria.



Figure 6.

Microsomal vitamin D–25‐hydroxylase enzyme.

From DeLuca 56


Figure 7.

Formation of 1,25‐dihydroxyvitamin D3 and 24R,25‐dihydroxyvitamin D3 from 25‐hydroxyvitamin D3 in renal mitochondria.



Figure 8.

25‐Hydroxyvitamin D3–1α‐hydroxylase system in chick renal mitochondria.

From DeLuca 56


Figure 9.

The metabolism of 1,25‐dihydroxyvitamin D3.

From Kumar 125


Figure 10.

Physiological adaptations to hypo‐ and hypercalcemia. PTH, parathyroid hormone; CT, calcitonin.



Figure 11.

Physiological adaptations to hypo‐ and hyperphosphatemia.



Figure 12.

Thermodynamic considerations in absorption of calcium in intestinal cell.

From Wasserman 245
References
 1. Adams, N. D., T. L. Garthwaite, R. W. Gray, T. C. Hagen, and J. Lemann, Jr. The interrelationships among prolactin, 1,25‐dihydroxyvitamin D3 and parathyroid hormone in humans. J. Clin. Endocrinol. Metab. 49: 628–630, 1979.
 2. Adams, N., R. W. Gray, and J. Lemann, Jr. The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25‐dihydroxyvitamin D. Calcif. Tissue Int. 28: 233–238, 1979.
 3. Adams, N. D., R. W. Gray, and J. Lemann, Jr. The effects of oral CaCO3 loading and dietary calcium deprivation on plasma 1,25‐dihydroxyvitamin D concentrations in healthy adults. J. Clin. Endocrinol. Metab. 48: 1008–1016, 1979.
 4. Akiba, T., G. Endou, C. Koseki, F. Sakai, N. Horiuchi, and T. Suda. Localization of 25‐hydroxyvitamin D3–lα‐hydroxylase activity in the mammalian kidney. Biochem. Biophys. Res. Commun. 94: 313–318, 1980.
 5. Allegretto, E. A., and J. W. Pike. Trypsin cleavage of chick 1,25‐dihydroxyvitamin D3 receptors: generation of discrete polypeptides which retain hormone but are unreactive to DNA and monoclonal antibody. J. Biol. Chem. 260: 10139–10145, 1985.
 6. Audran, M., and R. Kumar. The physiology and pathophysiology of vitamin D. Mayo. Clin. Proc. 60: 851–866, 1985.
 7. Baksi, S. N., and A. D. Kenny. Acute effect of estradiol on the renal vitamin D hydroxylases in Japanese quail. Biochem. Pharmacol. 27: 2765–2768, 1978.
 8. Baksi, S. N., and A. D. Kenny. Acute effect of parathyroid extract on renal vitamin D hydroxylases in Japanese quail. Pharmacology 18: 169–174, 1979.
 9. Baksi, S. N., and A. D. Kenny. Estradiol‐induced stimulation of 25‐hydroxyvitamin D3–1‐hydroxylase in vitamin D–deficient Japanese quail. Pharmacology 20: 298–303, 1980.
 10. Baksi, S. N., A. D. Kenny, S. M. Galli‐Gallardo, and P.K.T. Pang. Vitamin D metabolism in bullfrogs and Japanese quail: effects of estradiol and prolactin. Gen. Comp. Endocrinol. 35: 258–262, 1978.
 11. Bar, A., and S. Hurwitz. Relationship of intestinal and plasma calcium binding protein to intestinal calcium absorption. FEBS Lett. 102: 79–81, 1979.
 12. Baran, D. T., S. W. Lee, O. D. Jo, and L. V. Avioli. Acquired alterations in vitamin D metabolism in the acidotic state. Calcif. Tissue Int. 34: 165–168, 1982.
 13. Bauveur, B., M. Garabedian, C. Fellot, P. Mougin, and S. Balsan. The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks. Calcif. Tissue Res. 23: 121–124, 1977.
 14. Bell, N. H., Sarcoidosis, In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nihjoff, 1984, p. 579–589.
 15. Bhattacharyya, M. H., and H. F. DeLuca. The regulation of rat calciferol‐25‐hydroxylase. J. Biol. Chem. 248: 2969–2973, 1973.
 16. Bhattacharyya, M. H., and H. F. DeLuca. Subcellular location of rat liver calciferol–25‐hydroxylase. Arch. Biochem. Biophys. 160: 58–62, 1974.
 17. Bikle, D. D., E. Gee, B. Halloran, and J. G. Haddad. Free 1,25‐dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J. Clin. Invest. 74: 1966–1971, 1984.
 18. Bikle, D. D., P. K. Siiteri, E. Ryzen, J. G. Haddad, and E. Gee. Serum protein binding of 1,25‐dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J. Clin. Endocrinol. Metab. 61: 969–975, 1985.
 19. Bikle, D. D., D. T. Zolock, R. L. Morrissey, and R. H. Herman. Independence of 1,25‐dihydroxyvitamin D3–mediated calcium transport from de novo RNA and protein synthesis. J. Biol. Chem. 253: 484–488, 1978.
 20. Bilezikian, J. P., R. E. Canfield, T. P. Jacobs, J. S. Polay, A. P. D'Adamo, J. A. Eisman, and H. F. DeLuca. Response of 1α,25‐dihydroxyvitamin D3 to hypocalcemia in human subjects. N. Engl. J. Med. 299: 437–441, 1978.
 21. Birge, S. J., and D. H. Alpers. Stimulation of intestinal muscle proliferation by vitamin D. Gastroenterology 64: 977–982, 1973.
 22. Bishop, C. W., N. C. Kendrick, M. C. Dame, and H. F. DeLuca. 1α,25‐Dihydroxyvitamin D–induced modification of a cytosolic protein in embryonic chick intestine. J. Biol. Chem. 260: 5209–5212, 1985.
 23. Bjorkhem, I., and I. Holmberg. On the 25‐hydroxylation of vitamin D3 in vitro studied with a mass fragmentographic technique. J. Biol. Chem. 254: 9518–9524, 1979.
 24. Blomhoff, R., P. Helgerud, S. Dueland, T. Berg, J. I. Pederson, K. R. Norum, and C. A. Drevon. Lymphatic absorption and transport of retinol and vitamin D3 from rat intestine: evidence for different pathways. Biochim. Biophys. Acta. 772: 109–116, 1984.
 25. Blunt, J. W., and H. F. DeLuca. The synthesis of 25‐hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry 8: 671–675, 1969.
 26. Blunt, J. W., H. F. DeLuca, and H. K. Schnoes. 25‐Hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry 7: 3317–3322, 1968.
 27. Bonjour, J.‐P., C. Preston, and H. Fleisch. Effect of 1,25‐dihydroxyvitamin D3 on the renal handling of Pi in thyroparathyroidectomized rats. J. Clin. Invest. 60: 1419–1428, 1977.
 28. Bouillon, R., E. Muls, and P. de Moor. Influence of thyroid function on the serum concentration of 1,25‐dihydroxyvitamin D3. J. Clin. Endocrinol. Metab. 51: 793–797, 1980.
 29. Bouillon, R., F. A. Van Assche, E. Van Baelen, W. Heyns, and P. de Moor. Influence of the vitamin D–binding protein on the serum concentration of 1,25‐dihydroxyvitamin D3: significance of the free 1,25‐dihydroxyvitamin D3 concentration. J. Clin. Invest. 67: 589–596, 1981.
 30. Boyle, I. T., R. W. Gray, and H. F. DeLuca. Regulation by calcium of in vivo synthesis of 1,25‐dihydroxycholecalciferol and 21,25‐dihydroxycholecalciferol. Proc. Natl. Acad. Sci. USA 68: 2131–2134, 1971.
 31. Boyle, I. T., R. W. Gray, J. L. Omdahl, and H. F. DeLuca. Calcium control of the in vivo biosynthesis of 1,25‐dihydroxyvitamin D3: Nicolaysen's endogenous factor. In: Proc. Int. Symp. Endocrinol., 3rd, 1971. London: Heinemann, 1972, p. 468–476.
 32. Brickman, A. S., J. W. Coburn, S. G. Massry, and A. W. Norman. 1,25‐Dihydroxyvitamin D3 in normal man and patients with renal failure. Ann. Intern. Med. 80: 161–168, 1974.
 33. Brown, D. J., E. Spanos, and I. MacIntyre. Role of pituitary hormones in regulating renal vitamin D metabolism in man. Br. Med. J. 280: 277–278, 1980.
 34. Brumbaugh, P. F., and M. R. Haussler. 1α,25‐Dihydroxycholecalciferol receptors in intestine. I. Association of 1α,25‐dihydroxycholecalciferol with intestinal mucosa chromatin. J. Biol. Chem. 249: 1251–1257, 1974.
 35. Brumbaugh, P. F., and M. R. Haussler. 1α, 25‐Dihydroxycholecalciferol receptors in intestine. II. Temperature‐dependent transfer of the hormone to chromatin via a specific cytosol receptor. J. Biol. Chem. 249: 1258–1262, 1974.
 36. Brunette, M. G., M. Chan, C. Ferriere, and K. D. Roberts. Site of 1,25(OH)2 vitamin D3 synthesis in the kidney. Nature 276: 287–289, 1978.
 37. Burnatowska, M. A., C. A. Harris, R. A. L. Sutton, and J. F. Seely. Effects of vitamin D on renal handling of calcium, magnesium, and phosphate in the hamster. Kidney Int. 27: 864–870, 1985.
 38. Bushinsky, D. A., M. J. Favus, A. B. Schneider, P. K. Sen, L. M. Sherwood, and F. L. Coe. Effects of metabolic acidosis on PTH and 1,25(OH)2D3 response to low calcium diet. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F570–F575, 1982.
 39. Carre, M., O. Ayigbede, L. Miravet, and H. Rasmussen. The effect of prednisolone upon the metabolism and action of 25 hydroxy and 1,25 dihydroxy vitamin D3. Proc. Natl. Acad. Sci. USA 71: 2996–3000, 1974.
 40. Castillo, L., Y. Tanaka, H. F. DeLuca, and M. L. Sunde. The stimulation of 25‐hydroxyvitamin D3–1α‐hydroxylase by estrogen. Arch. Biochem. Biophys. 179: 211–217, 1977.
 41. Chen, T. C, L. Castillo, M. Korycka‐Dahl, and H. F. DeLuca. Role of vitamin D metabolites in phosphate transport in rat intestine. J. Nutr. 104: 1056–1060, 1974.
 42. Chesney, R. W., A. J. Hamstra, R. B. Mazess, H. F. DeLuca, and S. O'Reagan. Reduction of serum 1,25‐dihydroxyvitamin D3 in children receiving glucocorticoids. Lancet 2: 1123–1125, 1978.
 43. Chick, H., E. J. Palzell, and E. M. Hume. Studies of Rickets in Vienna 1919–1922. Medical Research Council, Special Report No. 77, 1923.
 44. Clemens, T. L., L. J. Fraher, L. M. Sandler, and J. L. H. O'Riordan. Detection of 1,24,25‐trihydroxyvitamin D3 in human serum by radioimmunoassay. In: Hormonal Control of Calcium Metabolism, edited by D. V. Cohn, R. V. Talmadge, and J. L. Mathews. Amsterdam: Excerpta Medica, 1981, p. 366.
 45. Clemens, T. L., S. L. Henderson, J. S. Adams, and M. F. Holick. Increased skin pigmentation reduces the capacity of skin to synthesize vitamin D3. Lancet 1: 74–76, 1982.
 46. Cooke, N. W., and E. V. Davik. Serum vitamin D–binding protein is a third member of the albumin α‐fetoprotein gene family. J. Clin Invest. 76: 2420–2424, 1985.
 47. Cooke, N. E., J. Walgate, and J. G. Haddad, Jr. Human serum binding protein for vitamin D and its metabolites. I. Physiochemical and immunological identification in human tissues. J. Biol. Chem. 254: 5958–5964, 1979.
 48. Cooke, N. E., J. Walgate, and J. G. Haddad, Jr. Human serum binding protein for vitamin D and its metabolites. II. Specific, high affinity association with a protein in nucleated tissue. J. Biol. Chem. 254: 5965–6971, 1979.
 49. Corradino, R. A. 1,25‐Dihydroxycholecalciferol: inhibition of action in organ‐cultured intestine by actinomycin D and α‐amanitin. Nature 243: 42–43, 1973.
 50. Corradino, R. A. Embryonic chick intestine in organ culture: interaction of adenylate cyclase system and vitamin D3‐mediated calcium absorptive mechanism. Endocrinology 94: 1607–1614, 1974.
 51. Costanzo, L. S., P. R. Sheehe, and I. M. Weiner. Renal actions of vitamin D in D‐deficient rats. Am. J. Physiol. 226: 1490–1495, 1974.
 52. Crivello, J. F. Bovine renal mitochondrial vitamin D3 hydroxylases: regulation of in vitro activities by inhibitors and antioxidants. Endocrinology 117: 447–456, 1985.
 53. Davie, M. Calcium‐ion–binding activity in human small‐intestinal mucosal cytosol: purification of two proteins and interrelationship of calcium fractions. Biochem. J. 197: 55–65, 1981.
 54. Davis, W. L., and R. G. Jones. Lysosomal proliferation in rachitic avian intestinal absorptive cells following 1,25‐dihydroxycholecalciferol. Tissue Cell 14: 585–595, 1982.
 55. DeJonge, H. R., W. E. J. Ghijsen, and C. H. Van Os. Phosphorylated intermediates of Ca2+‐ATPase and alkaline phosphatase in plasma membranes from rat duodena epithelium. Biochim. Biophys. Acta 647: 140–149, 1981.
 56. DeLuca, H. F., The metabolism, physiology, and function of vitamin D. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 1–68.
 57. DeLuca, H. F., and H. K. Schnoes. Metabolism and mechanism of action of vitamin D. Annu. Rev. Biochem. 45: 631–665, 1976.
 58. DeLuca, H. F., and H. K. Schnoes. Vitamin D: recent advances. Annu. Rev. Biochem. 52: 411–439, 1983.
 59. Desplan, C, O. Heidmann, J. W. Lillie, C. Auffray, and M. Thomasset. Sequence of rat intestinal vitamin D–dependent calcium‐binding protein derived from a cDNA clone. Evolutionary implications. J. Biol. Chem. 258: 13502–13505, 1983.
 60. Desplan, C., M. Thomasset, and M. Moukhtar. Synthesis, molecular cloning, and restriction analysis of DNA complementary to vitamin D–dependent calcium‐binding protein mRNA from rat duodenum. J. Biol. Chem. 258: 2762–2765, 1983.
 61. Dokoh, S., M. R. Haussler, and J. W. Pike. Development of a radioligand immunoassay for 1,25‐dihydroxychoecalciferol receptors utilizing monoclonal antibody. Biochem. J. 221: 129–136, 1984.
 62. Drezner, M. K., F. A. Neelon, R. Haussler, H. T. Mc‐Pherson, and H. E. Lebovitz. 1,25‐Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism. J. Clin. Endocrinol. Metab. 42: 621–628, 1976.
 63. Dueland, S., J. I. Peterson, P. Helgerud, and C. A. Drevon. Transport of vitamin D3 from rat intestine: evidence for transfer of vitamin D3 from chylomicrons to α‐globulins. J. Biol. Chem. 257: 146–150, 1982.
 64. Eisman, J. A., 1,25‐Dihydroxyvitamin D3 receptor and role of 1,25‐(OH)2D3 in human cancer cells. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 365–382.
 65. Eisman, J. A., and H. F. DeLuca. Intestinal 1,25‐dihydroxy‐vitamin D3 binding protein: specificity of binding. Steroids. 30: 245–257, 1977.
 66. Eisman, J. A., J. D. Wark, R. L. Price, and J. M. Mosely. Modulation of 1,25‐dihydroxyvitamin D in man by stimulation and suppression tests. Lancet 2: 931–933, 1979.
 67. Emmersten, K., F. Melsen, L. Mosekilde, B. I. Lund, B. J. Lund, O. H. Sorensen, H. E. Nielsen, H. Solling, and H. H. Hansen. Altered vitamin D metabolism and bone remodelling in patients with medullary thyroid carcinoma and hypercalcitoninemia. Metab. Bone Dis. Rel. Res. 4: 17–23, 1981.
 68. Eskildsen, P. C., B. J. Lund, O. H. Sorensen, B. I. Lund, J. E. Bishop, and A. W. Norman. Acromegaly and vitamin D metabolism: effect of bromocriptine treatment. J. Clin Endocrinol. Metab. 49: 484–486, 1979.
 69. Esvelt, R., and H. F. DeLuca. Calcitroic acid: biological activity and tissue distribution studies. Arch. Biochem. Biophys. 206: 403–413, 1981.
 70. Esvelt, R., H. K. Schnoes, and H. F. DeLuca. Vitamin D3 from rat skins irradiated in vitro with ultraviolet light. Arch. Biochem. Biophys. 188: 282–286, 1978.
 71. Esvelt, R. P., H. K. Schnoes, and H. F. DeLuca. Isolation and characterization of 1α‐hydroxy‐23‐carboxytetranor‐vitamin D: a major metabolite of 1,25‐dihydroxyvitamin D3. Biochemistry 18: 3977–3983, 1979.
 72. Fainaru, M., and J. Silver. A method for studying plasma transport of vitamin D applicable to hypervitaminosis D. Clin Chim. Acta 91: 303–307, 1979.
 73. Favus, M. M., M. W. Walling, and D. V. Kimberg. Effects of 1,25‐dihydroxy‐cholecalciferol on intestinal calcium transport in cortisone‐treated rats. J. Clin. Invest. 52: 1680–1685, 1973.
 74. Feher, J. J., and R. H. Wasserman. Intestinal calcium‐binding protein and calcium absorption in cortisol treated chicks: effects of vitamin D3 and 1,25‐dihydroxyvitamin D3. Endocrinology 104: 547–551, 1979.
 75. Fontaine, O., T. Matsumoto, D. B. P. Goodman, and H. Rasmussen. Liponomic control of Ca2+ transport: relationship to mechanism of action of 1,25‐dihydroxyvitamin D3. Proc. Natl. Acad. Sci USA 78: 1751–1754, 1981.
 76. Franceschi, R. T., and H. F. DeLuca. The effect of inhibitors of protein and RNA synthesis on 1α,25‐dihydroxyvitamin D3‐dependent calcium uptake in cultured embryonic chick duodenum. J. Biol. Chem. 256: 3848–3852, 1981.
 77. Fraser, D. R., and E. Kodicek. Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature. 228: 764–766, 1970.
 78. Fraser, D. R., and E. Kodicek. Regulation of 25‐hydroxy‐cholecalciferol–1‐hydroxylase activity in kidney by parathyroid hormone. Nature [New Biol.]. 241: 163–166, 1973.
 79. Freedman, R. A., M. M. Weiser, and K. J. Isselbacher. Calcium translocation by Golgi and lateral–basal vesicles from rat intestine: decrease in vitamin D–deficient rats. Proc. Natl. Acad. Sci. USA 74: 3612–3616, 1977.
 80. Fullmer, C. S., and R. H. Wasserman. The amino acid sequence of bovine intestinal calcium‐binding protein. J. Biol. Chem. 256: 5669–5674, 1981.
 81. Fullmer, C. S., and R. H. Wasserman. Chicken intestinal 280‐kilodalton calbindin‐D: complete amino acid sequence and structural considerations. Proc. Natl. Acad. Sci. USA 84: 4772–4776, 1987.
 82. Gafter, U., J. A. Kraut, D. B. N. Lee, V. Silis, M. W. Walling, K. Kurokawa, M. R. haussler, and J. W. Coburn. Effect of metabolic acidosis on intestinal absorption of calcium and phosphorus. Am. J. Physiol. 239 (Gastrointest. Liver Physiol. 2): G480–G484, 1980.
 83. Garabedian, M., M. F. Holick, H. F. DeLuca, and I. T. Boyle. Control of 25‐hydroxycholecalciferol metabolism by the parathyroid glands. Proc. Natl. Acad. Sci. USA 69: 1673–1676, 1972.
 84. Gertner, J. M., R. L. Horst, A. E. Broadus, H. Rasmussen, and M. Genel. Parathyroid function and vitamin D metabolism during human growth hormone replacement. J. Clin. Endocrinol. Metab. 49: 185–188, 1979.
 85. Ghazarian, J. G., and H. F. DeLuca. 25‐Hydroxycholecal‐ciferol–1‐hydroxylase: a specific requirement for NADPH and a hemoprotein component in chick kidney mitochondria. Arch. Biochem. Biophys. 160: 63–72, 1974.
 86. Ghazarian, J. G., C. R. Jefcoate, J. C. Knutson, W. H. Orme‐Johnson, and H. F. DeLuca. Mitochondrial cytochrome P450: a component of chick kidney 25‐hydroxycho‐lecalciferol–1α‐hydroxylase. J. Biol. Chem. 249: 3026–3033, 1974.
 87. Ghazarian, J. G., B. Kream, K. M. Botham, M. W. Nickells, and H. F. DeLuca. Rat plasma 25‐hydroxyvitamin D3 binding protein: an inhibitor of the 25‐hydroxyvitamin D3–1α‐hydroxylase. Arch. Biochem. Biophys. 189: 212–220, 1978.
 88. Ghijsen, W. E. J. M., and C. H. Van Os. 1,25‐Dihydroxy‐vitamin D3 regulates ATP‐dependent calcium transport in basolateral plasma membranes of rat enterocytes. Biochim. Biophys. Acta 689: 170–172, 1982.
 89. Gloor, H. J., J.‐P. Bonjour, J. Caverzasio, and H. Fleisch. Resistance to the phosphaturic and calcemic actions of parathyroid hormone during phosphate depletion: prevention by 1,25‐dihydroxyvitamin D3. J. Clin. Invest. 63: 371–377, 1979.
 90. Gray, R. W., A. E. Caldas, D. R. Wilz, J. Lemann, Jr., G. A. Smith, and H. F. DeLuca. Metabolism and excretion of 3H‐1,25‐(OH)2‐vitamin D3 in healthy adults. J. Clin. Endocrinol. Metab. 46: 756–765, 1978.
 91. Gray, R. W., and T. L. Garthwaite. Activation of renal 1,25‐dihydroxyvitamin D3 synthesis by phosphate deprivation: evidence for a role for growth hormone. Endocrinology 116: 189–193, 1985.
 92. Gray, R. W., T. L. Garthwait, and L. S. Phillips. Growth hormone and triiodothyronine permit an increase in plasma 1,25(OH)2D concentrations in response to dietary phosphate deprivation in hypophysectomized rats. Calcif. Tissue Int. 35: 100–106, 1983.
 93. Gray, R. W., M. L. Haasch, and C. E. Brown. Regulation of plasma 1,25‐(OH)2D3 by phosphate: evidence against a role for total or acid‐soluble renal phosphate content. Calcif. Tissue Int. 35: 773–777, 1983.
 94. Gray, R. W., J. L. Omdahl, J. G. Ghazarian, and H. F. DeLuca. 25‐Hydroxycholecalciferol–1‐hydroxylase: subcellular location and properties. J. Biol. Chem. 247: 7528–7532, 1972.
 95. Gray, R. W., D. R. Wilz, A. E. Caldas, and J. Lemann, Jr. The importance of phosphate in regulating plasma, 1,25‐(OH)2‐vitamin D levels in humans: studies in healthy subjects, in calcium‐stone formers and in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 45: 299–306, 1977.
 96. Guillemant, J., and S. Guillemant. Early rise in cyclic GMP after 1,25‐dihydroxycholecalciferol administration in the chick intestinal mucosa. Biochem. Biophys. Res. Commun. 93: 906–911, 1980.
 97. Haddad, J. G., Nature and functions of the plasma binding protein for vitamin D and its metabolites. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 383–396.
 98. Halloran, B. P., and H. F. DeLuca. Intestinal calcium transport: evidence for two distinct mechanisms of action of 1,25‐dihydroxyvitamin D3. Arch. Biochem. Biophys. 208: 477–486, 1981.
 99. Harnden, D. H., R. Kumar, M. F. Holick, and H. F. DeLuca. Side chain oxidation of 25‐hydroxy[26,27‐14C] vitamin D3 and 1,25‐dihydroxy[26,27‐14C] vitamin D3 in vivo. Science 193: 493–494, 1976.
 100. Harris, C. A., R. A. L. Sutton, and J. F. Seely. Effect of 1,25‐(OH)2‐vitamin D3 on renal electrolyte handling in the vitamin D deficient rat: dissociation of calcium and sodium excretion. Clin Res. 24: 685A, 1976.
 101. Haussler, M. R., D. J. Baylink, M. R. Hughes, P. F. Brumbaugh, J. E. Wergedal, F. H. Shen, R. L. Nielsen, S. J. Counts, K. M. Bursac, and T. A. McCain. The assay of 1α,25‐dihydroxyvitamin D3: physiologic and pathophysiologic modulation of circulating hormone levels. Clin. Endocrinol. 5: 151s–165s, 1976.
 102. Haussler, M. R., D. W. Boyce, E. T. Littledike, and H. Rasmussen. A rapidly acting metabolite of vitamin D3. Proc. Natl. Acad. Sci. USA 68: 177–181, 1971.
 103. Haussler, M. R., and T. A. McCain. Basic and clinical concepts related to vitamin D metabolism and action. N. Engl. J. Med. 297: 974–983, 1041–1050, 1977.
 104. Henry, H. Regulation of the hydroxylation of 25‐hydroxyvitamin D3 in vivo and in primary cultures of chick kidney cells. J. Biol. Chem. 254: 2722–2729, 1979.
 105. Henry, H. Insulin permits parathyroid hormone stimulation of 1,25‐dihydroxyvitamin D3 production in cultured kidney cells. Endocrinology 108: 733–735, 1981.
 106. Henry, H. L. 25‐OH‐D3 metabolism in kidney cell cultures: lack of a direct effect of estradiol. Am. J. Physiol. 240 (Endocrinol. Metab. 3): E119–E124, 1981.
 107. Henry, L., Regulation of the synthesis of 1,25‐dihydroxyvitamin D3 and 24,25‐dihydroxyvitamin D3 in kidney cell culture. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 151–174.
 108. Hofmann, T., M. Kawakami, A. J. W. Hitchman, J. E. Harrison, and K. J. Dorrington. The amino acid sequence of porcine intestinal calcium‐binding protein. Can. J. Biochem. 57: 737–748, 1979.
 109. Holick, M. F., The photobiology of vitamin D3 in man. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 197–232.
 110. Holick, M. F., A. Kleiner‐Bossaller, H. K. Schnoes, P. J. Kasten, I. T. Boyle, and H. F. DeLuca. 1,24,25‐Trihydroxyvitamin D3. A metabolite of vitamin D3 effective on intestine. J. Biol. Chem. 248: 6691–6696, 1973.
 111. Holick, M. F., J. A. McLaughlin, M. B. Clark, S. A. Holick, J. T. Potts, Jr., R. R. Anderson, I. H. Blank, J. A. Parrish, and P. Elias. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210: 203–205, 1980.
 112. Holick, M. F., H. K. Schnoes, H. F. DeLuca, T. Suda, and R. J. Cousins. Isolation and identification of 1,25‐dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry 10: 2799–2804, 1971.
 113. Holick, S. A., M. St. Lezin, D. Young, S. Malaikal, and M. F. Holick. Isolation and identification of 24‐dehydroprovitamin D3 and its photolysis to 24‐dehydroprevitamin D3 in mammalian skin. J. Biol. Chem. 260: 12181–12184, 1985.
 114. Hove, K., R. L. Horst, E. T. Littledike, and D. C. Beitz. Infusions of parathyroid hormone in ruminants: hypercalcemia and reduced plasma 1,25‐dihydroxyvitamin D concentrations. Endocrinology 114: 897–903, 1984.
 115. Huldshinsky, K. Heilung von rachitis durch künstliche höhensonne. Dtsch. Med. Wochenschr. 45: 712–713, 1919.
 116. Insogna, K. L., A. E. Broadus, B. E. Dreyer, A. F. Ellison, and J. M. Gertner. Elevated production rate of 1,25‐dihydroxyvitamin D in patients with absorptive hypercalciuria. J. Clin. Endocrinol. Metab. 61: 490–495, 1985.
 117. Jande, S. S., and L. M. Brewer. Effects of vitamin D3 on duodenal absorption cells of chicks: an electron microscopic study. Z. Anat. Entwickl. Gesch. 144: 249–265, 1974.
 118. Kawashima, H., J. A. Kraut, and K. Kurokawa. Metabolic acidosis suppresses 25‐hydroxyvitamin D3‐1α‐hydroxylase in the rat kidney: distinct site and mechanism of action. J. Clin. Invest. 70: 135–140, 1982.
 119. Kawashima, H., and K. Kurokawa. Localization and hormonal regulation of 25(OH)D3–1α‐ and 24‐hydroxylases in the mammalian kidney. In: Vitamin D: Chemical, Biochemical and Clinical Endocrinology of Calcium Metabolism, edited by A. W. Norman, K. Schaefer, D. V. Herrath, and H.‐G. Grigoleit. Berlin: Walter de Gruyter, 1982, p. 449–454.
 120. Kawashima, H., S. Torikai, and K. Kurokawa. Calcitonin selectively stimulates 25‐hydroxyvitamin D3–1α‐hydroxylase in proximal straight tubule of rat kidney. Nature 291: 327–329, 1981.
 121. Kawashima, H., S. Torikai, and K. Kurokawa. Localization of 25‐hydroxyvitamin D3 1α‐hydroxylase and 24‐hydroxylase along the rat nephron. Proc. Natl. Acad. Sci USA 78: 1199–1203, 1981.
 122. Kimberg, D. V., R. D. Baerg, E. Gershon, and R. T. Grandusius. Effect of cortisone treatment on the active transport of calcium by the small intestine. J. Clin. Invest. 50: 1309–1321, 1971.
 123. Kowarski, S., and D. Schachter. Intestinal membrane calcium‐binding protein. Vitamin D–dependent membrane component of the intestinal calcium transport mechanism. J. Biol. Chem. 255: 10834–10840, 1980.
 124. Kumar, R. Hepatic and intestinal osteodystrophy and the hepatobiliary metabolism of vitamin D. Ann. Intern. Med. 98: 662–663, 1983.
 125. Kumar, R. The metabolism of 1,25‐dihydroxyvitamin D3. Physiol. Rev. 64: 478–504, 1984.
 126. Kumar, R. The metabolism and mechanism of action of 1,25‐dihydroxyvitamin D3. Kidney Int. 30: 793–803, 1986.
 127. Kumar, R., C. F. Abboud, and B. L. Riggs. The effect of elevated prolactin levels on plasma 1,25‐dihydroxyvitamin D and intestinal absorption of calcium. Mayo Clin. Proc. 55: 51–53, 1980.
 128. Kumar, R., W. R. Cohen, and F. H. Epstein. Vitamin D and calcium hormones in pregnancy. N. Engl. J. Med. 302: 1143–1145, 1980.
 129. Kumar, R., W. R. Cohen, P. Silva, and F. H. Epstein. Elevated 1,25‐dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J. Clin. Invest. 63: 342–344, 1979.
 130. Kumar, R., and H. F. DeLuca. Side chain oxidation of 1,25‐dihydroxyvitamin D3 in the rat: effect of removal of the intestine. Biochem. Biophys. Res. Commun. 76: 253–258, 1977.
 131. Kumar, R., D. H. Harnden, and H. F. DeLuca. Metabolism of 1,25‐dihydroxyvitamin D3: evidence for side chain oxidation. Biochemistry 15: 2420–2423, 1976.
 132. Kumar, R., J. M. Londowski, M. Pass Murari, and S. Nagubandi. Synthesis and biological activity of vitamin D2 3β‐glucosiduronate and vitamin D2 3β‐sulfate: role of vitamin D2 conjugates in calcium homeostasis. J. Steroid Biochem. 17: 495–502, 1982.
 133. Kumar, R., T. J. Merimee, P. Silva, and F. H. Epstein. The effect of chronic growth hormone excess or deficiency on plasma 1,25‐dihydroxyvitamin D levels in man. In: Proc. 4th Workshop Vitamin D. Elmsford, NY: Walter de Gruyter, 1979, p. 1005–1009.
 134. Kumar, R., S. Nagubandi, V. R. Mattox, and J. M. Londowski. Enterohepatic physiology of 1,25‐dihydroxyvitamin D3. J. Clin. Invest. 65: 277–284, 1980.
 135. Kumar, R., H. K. Schnoes, and H. F. DeLuca. Rat intestinal 25‐hydroxyvitamin D3 and 1α,25‐dihydroxyvitamin D3–24‐hydroxylase. J. Biol. Chem. 253: 3804–3809, 1978.
 136. Kurnik, B. R. C., and K. A. Hruska. Mechanism of stimulation of renal phosphate transport by 1,25‐dihydroxycholecalciferol. Biochim. Biophys. Acta 817: 42–50, 1985.
 137. Lane, S. M., and D. E. M. Lawson. Differentiation of the changes in alkaline phosphatase from calcium ion–activated adenosine triphosphatase activities associated with increased calcium absorption in chick intestine. Biochem. J. 174: 1067–1070, 1978.
 138. Larkins, R. G., S. J. MacAules, A. Rapoport, T. J. Marfin, B. R. Tullock, P. G. H. Byfield, E. W. Mathews, and I. MacIntyre. Effects of nucleotides, hormones, ions and 1,25‐dihydroxycholecalciferol on 1,25‐dihydroxycholecalciferol production in isolated tubules. Clin. Sci. Mol. Med. 46: 569–583, 1974.
 139. Lawson, D. E. M., D. R. Fraser, E. Kodicek, H. R. Morris, and D. H. Williams. Identification of 1,25‐dihydroxycholecalciferol, a new kidney hormone controlling calcium metabolism. Nature 230: 228–230, 1971.
 140. Lee, S. W., J. Russell, and L. V. Avioli. 25‐Hydroxycholecalciferol to 1,25‐dihydroxycholecalciferol: conversion impaired by systemic metabolic acidosis. Science 195: 994–996, 1977.
 141. Litwiller, R., D. Fass, and R. Kumar. The amino acid sequence of the NH2‐terminal portion of rat and human vitamin D binding protein: evidence for a high degree of homology between rat and human vitamin D binding protein. Life Sci. 38: 2179–2184, 1986.
 142. Litwiller, R. D., V. R. Mattox, I. Jardine, and R. Kumar. Evidence for a monoglucuronide of 1,25‐dihydroxyvitamin D3 in rat bile. J. Biol. Chem. 257: 7491–7494, 1982.
 143. Londowski, J. M., S. Bollman Kost, M. Gross, L. Labler, W. Meier, and R. Kumar. Biologic activity of 3β‐D‐glucopyranosides of vitamin D compounds. J. Pharmacol. Exp. Ther. 234: 25–29, 1985.
 144. Londowski, J. M., S. Bollman Kost, W. Meier, L. Labler, and R. Kumar. The biological activity of the C‐1, C‐3, C‐25 β‐D‐glucopyranosides of 1,25‐dihydroxyvitamin D3. J. Pharmacol. Exp. Ther. 237: 837–840, 1986.
 145. Londowski, J. M., L. K. Revelle, S. B. Kost, R. A. Corradino, and R. Kumar. Synthesis and biologic activity of 3β‐thiovitamin D3. J. Steroid Biochem. 23: 81–85, 1985.
 146. Lorenc, R., Y. Tanaka, H. F. DeLuca, and G. Jones. Lack of effect of calcitonin on the regulation of vitamin D metabolism in the rat. Endocrinology 100: 468–472, 1977.
 147. Lufkin, E. G., R. Kumar, and H. Heath, III. Hyperphosphatemic tumoral calcinosis: effects of phosphate depletion on vitamin D metabolism and of acute hypocalcemia on parathyroid hormone secretion and action. J. Clin. Invest. 56: 1319–1322, 1983.
 148. Lund, B. J., O. H. Sorensen, B. I. Lund, J. E. Bishop, and A. W. Norman. Stimulation of 1,25‐dihydroxyvitamin D production by parathyroid hormone and hypocalcemia in man. J. Clin. Endocrinol. Metab. 50: 480–484, 1980.
 149. Lund, B. J., O. H. Sorensen, B. I. Lund, J. E. Bishop, and A. W. Norman. Vitamin D metabolism in hypoparathyroidism. J. Clin. Endocrinol. Metab. 51: 606–610, 1980.
 150. Madhok, T. C., and H. F. DeLuca. Characteristics of the rat liver microsomal enzyme converting cholecalciferol into 25‐hydroxycholecalciferol. Evidence for participation of a cytochrome P‐450. Biochem. J. 184: 491–499, 1979.
 151. Martin, D. L., and H. F. DeLuca. Influence of sodium on calcium transport by the rat small intestine. Am. J. Physiol. 216: 1351–1359, 1969.
 152. Martin, D. L., M. J. Melancon, Jr., and H. F. DeLuca. Vitamin D stimulated, calcium‐dependent adenosine triphosphatase from brush borders of rat small intestine. Biochem. Biophys. Res. Commun. 35: 819–823, 1969.
 153. Marx, S. J., Resistance to vitamin D. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 721–745.
 154. Matsumoto, T., O. Fontaine, and H. Rasmussen. Effect of 1,25‐dihydroxyvitamin D3 on phospholipid metabolism in chick duodenal mucosal cell. J. Biol. Chem. 256: 3354–3360, 1981.
 155. Mayer, E., J. E. Bishop, R. A. S. Chandraratna, W. H. Okamura, J. R. Kruse, G. Popjak, N. Ohnuma, and A. W. Norman. Isolation and identification of 1,25‐dihydroxy‐24‐oxo‐vitamin D3 and 1,23,25‐trihydroxy24‐oxo‐vitamin D3. J. Biol. Chem. 258: 13458–13465, 1983.
 156. McCarthy, J. T., S. S. Barham, and R. Kumar. 1,25‐Dihydroxyvitamin D3 rapidly alters the morphology of the duodenal mucosa of rachitic chicks: evidence for novel effects of 1,25‐dihydroxyvitamin D3. J. Steroid Biochem. 21: 253–258, 1984.
 157. McDonnell, D. P., D. J. Mangelsdorf, J. W. Pike, M. R. Haussler, B. W. O'Malley. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235: 1214–1217, 1987.
 158. McLaughlin, J. A., R. R. Anderson, and M. F. Holick. Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science 216: 1001–1003, 1982.
 159. McLaughlin, J. A., M. M. Weiser, and R. H. Freedman. Biphasic recovery of vitamin D–dependent Ca2+ uptake by rat intestinal Golgi membranes. Gastroenterology 78: 325–332, 1980.
 160. Melancon, M. J., Jr., and H. F. DeLuca. Vitamin D stimulation of calcium‐dependent adenosine triphosphatase in chick intestinal brush borders. Biochemistry 9: 1658–1664, 1970.
 161. Meyer, S. A., and R. H. Wasserman. Vitamin D3 increases ATP‐dependent calcium transport of chick duodenal basolateral membranes. Federation Proc. 42: 1367, 1983.
 162. Mezzetti, G., M. S. Moruzzi, and B. Barbiroli. Evidence for a 1,25‐dihydroxycholecalciferol–dependent spermine‐binding protein in chick duodenal mucosa. Biochem. Biophys. Res. Commun. 102: 287–294, 1981.
 163. Miller, A., III, and F. Bronner. Calcium uptake in isolated brush‐border vesicles from rat small intestine. Biochem. J. 196: 391–401, 1981.
 164. Mosekilde, B. J., F. Melsen, B. I. Lund, B. J. Lund, and O. H. Sorensen. Serum levels of vitamin D metabolites and bone remodelling in hyperthyroidism. Metabolism 31: 126–132, 1982.
 165. Nagubandi, S., R. Kumar, J. M. Londowski, R. A. Corradino, and P. S. Tietz. The role of vitamin D glucosiduronate in calcium homeostasis. J. Clin. Invest. 66: 1274–1280, 1980.
 166. Nagubandi, S., J. M. Londowski, S. Bollman, P. Tietz, and R. Kumar. Synthesis and biological activity of vitamin D3 3β‐sulfate: role of vitamin D3 sulfates in calcium homeostasis. J. Biol. Chem. 256: 5536–5539, 1981.
 167. Napoli, J. L., B. C. Pramanik, P. M. Royal, T. A. Reinhardt, and R. L. Horst. Intestinal synthesis of 24‐keto‐1,25‐dihydroxyvitamin D3. A metabolite with high affinity for the vitamin D cytosolic receptor. J. Biol. Chem. 258: 9100–9107, 1983.
 168. Nemere, I., C. S. Dunlap, and A. W. Norman. Studies on the mode of action of calciferol. XLVIII. Intestinal brush border topography: effects of vitamin D3 and filipin. Biochim. Biophys. Acta. 694: 307–327, 1982.
 169. Nordin, B. E. C., Calcium, phosphate and magnesium metabolism. In: Clinical Physiology and Diagnostic Procedures. New York: Churchill Livingstone, 1976.
 170. Norman, A. W., J. F. Myrtle, R. J. Midgett, H. G. Nowicki, V. Williams, and G. Popjak. 1,25‐Dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science 173: 51–54, 1971.
 171. Norman, A. W., J. A. Putkey, and I. Nemere. Intestinal calcium transport: pleiotropic effects mediated by vitamin D. Federation Proc. 41: 78–83, 1982.
 172. Nseir, N. I., J. Szramowski, and J. B. Puschett. Mechanism of the renal tubular effects of 25‐hydroxy and 1,25‐dihydroxy vitamin‐D3 in the absence of parathyroid hormone. Miner. Electrolyte Metab. 1: 48–56, 1978.
 173. O'Doherty, P. J. A. 1,25‐Dihydroxyvitamin D3 increases the activity of the intestinal phosphatidylcholine deacylation–reacylation cycle. Lipids 14: 75–77, 1979.
 174. Ohnuma, N., K. Bannai, H. Yamaguchi, Y. Hashimoto, and A. W. Norman. Isolation of a new metabolite of vitamin D produced in vivo: 1α,25‐dihydroxyvitamin D3‐26,23‐lactone. Arch. Biochem. Biophys. 204: 387–391, 1980.
 175. Olgaard, K., J. Schwartz, D. Finco, M. Arbelaez, J. Haddad, L. Avioli, S. Klahr, and E. Slatopolsky. Extraction of vitamin D metabolites by bones of normal adult dogs. J. Clin. Invest. 69: 684–690, 1982.
 176. Olson, E. B., Jr., J. C. Knutson, M. H. Bhattacharyya, and H. F. DeLuca. The effect of hepatectomy on the synthesis of 25‐hydroxyvitamin D3. J. Clin. Invest. 57: 1213–1220, 1976.
 177. Omdahl, J. L., R. W. Gray, I. T. Boyle, J. Knutson, and H. F. DeLuca. Regulation of metabolism of 25‐hydroxycholecalciferol by kidney tissue in vitro by dietary calcium. Nature [New Biol.] 237: 63–64, 1972.
 178. O'Regan, S., R. W. Chesney, A. Hamstra, J. A. Eisman, A. M. O'Gorman, and H. F. DeLuca. Reduced serum 1,25‐(OH)2 vitamin D3 levels in prednisone‐treated adolescents with systemic lupus erythematosus. Acta Paediatr. Scand. 68: 109–111, 1979.
 179. Orr, W. J., L. E. Holt, Jr., L. Wilkins, and F. H. Boone. The calcium and phosphorous metabolism in rickets, with special reference to ultraviolet ray therapy. Am. J. Dis. Child. 26: 362–372, 1923.
 180. Pahuja, D. N., and H. F. DeLuca. Thyroid hormone and vitamin D metabolism in the rat. Arch. Biochem. Biophys. 213: 293–298, 1982.
 181. Paulson, S. K., and H. F. DeLuca. Subcellular location and properties of rat renal 25‐hydroxyvitamin D3–1α‐hydroxylase. J. Biol. Chem. 260: 11488–11492, 1985.
 182. Pedersen, J. I., J. G. Ghazarian, N. R. Orme‐Johnson, and H. F. DeLuca. Isolation of chick renal mitochondrial ferredoxin active in the 25‐hydroxyvitamin D3–1α‐hydroxylase system. J. Biol. Chem. 251: 3933–3941, 1976.
 183. Pike, J. W. Evidence for a reactive sulfhydryl in the DNA binding domain of the 1,25‐dihydroxyvitamin D3 receptor. Biochem. Biophys. Res. Commun. 100: 1713–1719, 1981.
 184. Pike, J. W. Intestinal 1,25‐dihydroxyvitamin D3 receptors: hormone‐dependent uptake and saturability of nuclear components in vitro. Life Sci. 28: 957–963, 1981.
 185. Pike, J. W., S. Dokoh, M. R. Haussler, U. A. Liberman, S. J. Marx, and C. Eil. Vitamin D3–resistant fibroblasts have immunoassayable 1,25‐dihydroxyvitamin D3 receptors. Science 24: 879–881, 1984.
 186. Pike, J. W., C. A. Donaldson, S. L. Marion, and M. R. Haussler. Development of hybridomas secreting monoclonal antibodies to the chicken intestinal 1α,25‐dihydroxyvitamin D3 receptor. Proc. Natl. Acad. Sci. USA 79: 7719–7723, 1982.
 187. Pike, J. W., and M. R. Haussler. Purification of chicken intestinal receptor for 1,25‐dihydroxyvitamin D. Proc. Natl. Acad. Sci. USA 76: 5485–5489, 1979.
 188. Pike, J. W., and M. R. Haussler. Association of 1,25‐dihydroxyvitamin D3 with cultured 3T6 mouse fibroblasts: cellular uptake and receptor‐mediated migration to the nucleus. J. Biol. Chem. 258: 8554–8560, 1983.
 189. Pike, J. W., J. B. Parker, M. R. Haussler, A. Boass, and S. U. Toverud. Dynamic changes in circulating 1,25‐dihydroxy‐vitamin D during reproduction in rats. Science 204: 1427–1429, 1979.
 190. Ponchon, G., and H. F. DeLuca. The role of the liver in the metabolism of vitamin D. J. Clin. Invest. 48: 1273–1279, 1969.
 191. Popovitzer, M. M., J. B. Robinette, H. F. DeLuca, and M. F. Holick. The acute effect of 25‐hydroxycholecalciferol on renal handling of phosphorus: evidence for a parathyroid hormone–dependent mechanism. J. Clin. Invest. 53: 913–921, 1974.
 192. Puschett, J. B., W. S. Beck, Jr., and A. Jelonek. Parathyroid hormone and 25‐hydroxy vitamin D3: synergistic and antagonistic effects on renal phosphate transport. Science 190: 473–475, 1975.
 193. Puschett, J. B., P. C. Fernandez, I. T. Boyle, R. W. Gray, J. L. Omdahl, and H. F. DeLuca. The acute renal tubular effects of 1,25‐dihydroxycholecalciferol. Proc. Soc. Exp. Biol. Med. 141: 379–384, 1972.
 194. Puschett, J. B., J. Moranz, and W. S. Kurnick. Evidence for a direct action of cholecalciferol and 25‐hydroxycholecalciferol on the renal transport of phosphate, sodium, and calcium. J. Clin. Invest. 51: 373–385, 1972.
 195. Putkey, J. A., A. M. Spielvogel, R. D. Sauerheber, C. S. Dunlap, and A. W. Norman. Vitamin D‐mediated intestinal calcium transport. Effects of essential fatty acid deficiency and spin label studies of enterocyte membrane lipid fluidity. Biochim. Biophys. Acta. 688: 177–190, 1982.
 196. Rasmussen, H., O. Fontaine, E. E. Max, and D. B. P. Goodman. The effect of 1α‐hydroxyvitamin D3 administration on calcium transport in chick intestine brush border membrane vesicles. J. Biol. Chem. 254: 2993–2999, 1979.
 197. Rasmussen, H., T. Matsumoto, O. Fontaine, and D. B. P. Goodman. Role of changes in membrane lipid structure in the action of 1,25‐dihydroxyvitamin D3. Federation Proc. 41: 72–77, 1982.
 198. Rasmussen, H., E. E. Max, and D. B. P. Goodman. The effect of 1α‐OH‐D3 treatment on the structure and function of chick intestine border membrane. In: Vitamin D: Biochemical, Chemical and Clinical Aspects Related to Calcium Metabolism, edited by A. W. Norman, K. Schaefer, J. W. Coburn, H. F. DeLuca, D. Fraser, H.‐G. Grigoleit, and D. V. Herrath. New York: Walter de Gruyter, 1977. p. 913–915.
 199. Rasmussen, H., M. Wong, D. Bikle, and D. B. P. Goodman. Hormonal control of the renal conversion of 25‐hydroxycholecalciferol to 1,25‐dihydroxycholecalciferol. J. Clin. Invest. 51: 2502–2504, 1972.
 200. Reddy, G. S., G. Jones, S. W. Kook, and D. Fraser. Inhibition of 25‐hydroxyvitamin D3–1‐hydroxylase by chronic metabolic acidosis. Am. J. Physiol. 243 (Endocrinol. Metab. 6): E265–E271, 1982.
 201. Reeve, L., Y. Tanaka, and H. F. DeLuca. Studies on the site of 1,25‐dihydroxyvitamin D3 synthesis in vivo. J. Biol. Chem. 258: 3615–3617, 1983.
 202. Reinhardt, T. A., J. L. Napoli, D. C. Beitz, E. T. Little‐dike, and R. L. Horst. 1,24,25‐Trihydroxyvitamin D3: a circulating metabolite in vitamin D3–treated bovine. Arch. Biochem. Biophys. 213: 163–168, 1982.
 203. Reinhardt, T. A., J. L. Napoli, B. Pramanik, E. T. Little‐dike, D. C. Beitz, J. J. Partridge, M. R. Uskokovic, and R. L. Horst. 1α,25,26‐Trihydroxyvitamin D3: an in vivo and in vitro metabolite of vitamin D3. Biochemistry 20: 6230–6235, 1981.
 204. Revelle, L. K., J. M. Londowski, S. B. Kost, R. A. Corradino, and R. Kumar. Synthesis and biological activity of 3β‐fluorovitamin D3: comparison of the biological activity of 3β‐fluorovitamin D3 and 3‐deoxyvitamin D3. J. Steroid Biochem. 122: 469–474, 1985.
 205. Revelle, L., V. Solan, J. Londowski, S. Bollman, and R. Kumar. The synthesis and biologic activity of a C‐ring analog of vitamin D3: biologic and protein binding properties of 11α‐hydroxyvitamin D3. Biochemistry 23: 1983–1987, 1984.
 206. Roth, J., D. Brown, A. W. Norman, and L. Orci. Localization of the vitamin D–dependent calcium‐binding protein in mammalian kidney. Am. J. Physiol. 243 (Endocrinol. Metab. 6): E243–E252, 1982.
 207. Roth, J., B. Thorens, W. Hunziker, A. W. Norman, and L. Orci:. Vitamin D–dependent calcium‐binding protein: immunocytochemical localization in chick kidney. Science 214: 197–200, 1981.
 208. Sampson, H. W., and E. L. Krawitt. A morphometric investigation of the duodenal mucosa of normal, vitamin D–deficient, and vitamin D–replete rats. Calcif. Tissue Res. 21: 213–218, 1976.
 209. Schachter, D., and S. M. Rosen. Active transport of Ca45 by the female intestine and its dependence upon vitamin D. Am. J. Physiol. 176: 357–362, 1959.
 210. Seeman, E., R. Kumar, G. G. Hunder, M. Scott, H. Heath, III, and B. L. Riggs. Production, degradation and circulating levels of 1,25‐dihydroxyvitamin D in health and in chronic glucocorticoid excess. J. Clin. Invest. 66: 664–666, 1980.
 211. Seigfried, D., R. Kumar, J. Arruda, and N. A. Kurtzman. Influence of vitamin D on bicarbonate resorption. In: Proc. Int. Cong. Phosphate, 2nd, Heidelberg, 1975. New York: Plenum, 1976.
 212. Shiekh, M. S., A. Ramirez, M. Emmett, C. Santa Ana, L. R. Schiller, J. S. Fordtran. Role of vitamin D–dependent and vitamin D–independent mechanisms in absorption of food calcium. J. Clin. Invest. 81: 126–132, 1988.
 213. Shinki, T., N. Takahashi, T. Kadofuku, T. Sato, and T. Suda. Induction of spermidine N1‐acetyltransferase by 1α,25‐dihydroxyvitamin D3 as an early common event in the target tissues of vitamin D. J. Biol. Chem. 260: 2185–2190, 1985.
 214. Shinki, T., N. Takahashi, C. Miyaura, K. Samejima, Y. Nishii, and T. Suda. Ornithine decarboxylase activity in chick duodenum induced by 1α,25‐dihydroxycholecalciferol. Biochem. J. 195: 685–690, 1981.
 215. Shultz, T. D., S. Bollman, and R. Kumar. Decreased intestinal calcium absorption in vivo and normal brush border membrane vesicle calcium uptake in cortisol‐treated chickens: evidence for dissociation between calcium absorption and brush border vesicle uptake. Proc. Natl. Acad. Sci. USA 79: 3542–3546, 1982.
 216. Shultz, T. D., J. Fox, H. Heath, III, and R. Kumar. Do tissues other than the kidney produce 1,25‐dihydroxyvitamin D3 in vivo? A re‐examination. Proc. Natl. Acad. Sci. USA 80: 1746–1750, 1983.
 217. Simpson, R. U., and H. F. DeLuca. Purification of chicken intestinal receptor for 1α,25‐dihydroxyvitamin D3 to apparent homogeneity. Proc. Natl. Acad. Sci. USA 79: 16–20, 1982.
 218. Spanos, E., D. Barrett, I. MacIntyre, J. W. Pike, E. F. Safilian, and M. R. Haussler. Effect of growth hormone on vitamin D metabolism. Nature 273: 246–247, 1978.
 219. Spanos, E., K. W. Colston, A. Evans, L. S. Galante, S. J. MacAuley, and I. MacIntyre. Effect of prolactin on vitamin D metabolism. Nature 5: 163–167, 1976.
 220. Spencer, R., M. Charman, and D. E. M. Lawson. Stimulation of intestinal calcium‐binding–protein and mRNA synthesis in 1,25‐dihydroxycholecalciferol. Biochem. J. 175: 1089–1094, 1978.
 221. Spielvogel, A. M., R. D. Farley, and A. W. Norman. Studies on the mechanism of action of calciferol. V. Turnover time of check intestinal epithelial cells in reaction to the intestinal action of vitamin D. Exp. Cell Res. 74: 359–366, 1972.
 222. Staun, M., O. Noren, and H. Sjostrom. Ca2+‐binding protein from human kidney: purification and properties. Biochem. J. 217: 229–237, 1984.
 223. Steenbock, H., and A. Black. Fat soluble vitamins. VII. The induction of growth‐promoting and calcifying properties in a ration by exposure to ultraviolet light. J. Biol. Chem. 61: 405–422, 1924.
 224. Steeves, R. M., and D. E. M. Lawson. Effect of 1,25‐dihydroxyvitamin D on S‐adenosylmethionine decarboxylase in chick intestine. Biochim. Biophys. Acta 841: 292–298, 1985.
 225. Stumpf, W. E., M. Sar, R. A. Reid, Y. Tanaka, and H. F. DeLuca. Target cells for 1,25‐dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary and parathyroid. Science 206: 1188–1190, 1979.
 226. Sutton, R. A. L. 25‐Hydroxyvitamin D3 (25[OH]D3): enhancement of distal tubular calcium reabsorption in the dog. Kidney Int. 8: 404, 1975.
 227. Takahashi, N., T. Shinki, N. Kawate, K. Samejima, Y. Nishii, and T. Suda. Distribution of ornithine decarboxylase activity induced by 1α,25‐dihydroxyvitamin D3 in chick duodenal villus mucosa. Endocrinology 111: 1539–1551, 1982.
 228. Tanaka, Y., L. Castillo, H. F. DeLuca. Control of renal vitamin D hydroxylases in birds by sex hormones. Proc. Natl. Acad. Sci. USA 73: 2701–2705, 1976.
 229. Tanaka, Y., L. Castillo, and H. F. DeLuca. The 24‐hydroxylation of 1,25‐dihydroxyvitamin D3. J. Biol. Chem. 252: 1421–1424, 1977.
 230. Tanaka, Y., and H. F. DeLuca. Bone mineral mobilization activity of 1,25‐dihydroxyvitamin D3, a metabolite of vitamin D. Arch. Biochem. Biophys. 146: 574–578, 1971.
 231. Tanaka, Y., and H. F. DeLuca. The control of 25‐hydroxyvitamin D metabolism by inorganic phosphorus. Arch. Biochem. Biophys. 154: 566–574, 1973.
 232. Tanaka, Y., and H. F. DeLuca. Role of 1,25‐dihydroxyvitamin D3 in maintaining serum phosphorus and curing rickets. Proc. Natl. Acad. Sci. USA 71: 1040–1044, 1974.
 233. Tanaka, Y., and H. F. DeLuca. Stimulation of 24,25‐dihydroxyvitamin D3 production by 1,25‐dihydroxyvitamin D3. Science 183: 1198–1200, 1974.
 234. Tanaka, Y., B. Halloran, H. K. Schnoes, and H. F. DeLuca. In vitro production of 1,25‐dihydroxyvitamin D3 by rat placental tissue. Proc. Natl. Acad. Sci. USA 76: 5033–5035, 1979.
 235. Tanaka, Y., H. K. Schnoes, C. M. Smith, and H. F. DeLuca. 1,25,26‐Trihydroxyvitamin D3: isolation, identification and biological activity. Arch. Biochem. Biophys. 210: 104–109, 1981.
 236. Taylor, A. N., and R. H. Wasserman. Vitamin D3–induced calcium‐binding protein: partial purification, electrophoretic visualization and tissue distribution. Arch. Biochem. Biophys. 119: 536–540, 1967.
 237. Thomasset, M., C. O. Parkes, and P. Cuisinier‐Gleizes. Rat calcium‐binding proteins: distribution, development, and vitamin D dependence. Am. J. Physiol. 243 (Endocrinol. Metab. 6): E483–488, 1982.
 238. Trechsel, U., J.‐P. Bonjour, and H. Fleisch. Regulation of the metabolism of 25‐hydroxyvitamin D3 in primary cultures of chick kidney cells. J. Clin. Invest. 64: 206–217, 1979.
 239. Trechsel, U., J. A. Eisman, and J. A. Fischer. Calcium‐dependent, parathyroid hormone–independent regulation of 1,25‐dihydroxyvitamin D. Am. J. Physiol. 239 (Endocrinol. Metab. 2): E119–E124, 1980.
 240. Tsai, K.‐S., H. Heath, III, R. Kumar, and B. L. Riggs. Impaired vitamin D metabolism with aging in women: possible role in pathogenesis of senile osteoporosis. J. Clin. Invest. 73: 1668–1672, 1984.
 241. Van Baelen, H., R. Bouillon, and P. de Moor. Vitamin D–binding protein (Gc‐globulin) binds actin. J. Biol. Chem. 255: 2270–2272, 1980.
 242. Van Den Berg, C. J., R. Kumar, D. M. Wilson, H. Heath, III, and L. H. Smith. Orthophosphate therapy decreases urinary calcium excretion and serum 1,25‐dihydroxyvitamin D concentrations in idiopathic hypercalciuria. J. Clin. Endocrinol. Metab. 51: 998–1001, 1980.
 243. Warner, M. 25‐Hydroxyvitamin D hydroxylation: evidence for a dioxygenase activity of solubilized renal mitochondrial cytochrome P‐450. J. Biol. Chem. 258: 11590–11593, 1983.
 244. Wasserman, R. H., Molecular aspects of the intestinal absorption of calcium and phosphorus. In: Pediatric Diseases Related to Calcium, edited by H. F. DeLuca and C. S. Anast. New York: Elsevier, 1980, p. 107–132.
 245. Wasserman, R. H. Intestinal calcium absorption of calcium and phosphorus. Federation Proc. 40: 68–72, 1981.
 246. Wasserman, R. H., and M. E. Brindak. The effect of cholecalciferol on the phosphorylation of intestinal membrane proteins. In: Vitamin D: Basic Research and Its Clinical Application, edited by A. W. Norman, K. Schaefer, D. V. Herrath, H.‐G. Grigoleit, J. W. Coburn, H. F. DeLuca, E. G. Mawer, and T. Suda. New York: Walter de Gruyter, 1979, p. 703–710.
 247. Wasserman, R. H., M. E. Brindak, S. A. Meyer, and C. S. Fullmer. Evidence for multiple effects of vitamin D3 on calcium absorption: response of rachitic chicks, with or without partial vitamin D3 repletion, to 1,25‐dihydroxyvitamin D3. Proc. Natl. Acad. Sci. USA 79: 7939–7943, 1982.
 248. Wasserman, R. H., R. A. Corradino, and A. N. Taylor. Vitamin D–dependent calcium‐binding protein. Purification and some properties. J. Biol. Chem. 243: 3978–3986, 1968.
 249. Wasserman, R. H., C. S. Fullmer, and F. Shimura. Calcium absorption and the molecular effects of vitamin D3. In: Vitamin D: Basic and Clinical Aspects, edited by R. Kumar. Boston: Martinus Nijhoff, 1984, p. 233–257.
 250. Wasserman, R. H., and A. N. Taylor. Vitamin D–dependent calcium‐binding protein. Response to some physiological and nutritional variables. J. Biol. Chem. 243: 3987–3993, 1968.
 251. Weber, H., R. W. Gray, J. H. Sommghly, and J. Lemann. The lack of effect of chronic metabolic acidosis on 25‐OH‐vitamin D metabolism and serum parathyroid hormones in humans. J. Clin. Endocrinol. Metab. 43: 1047–1055, 1976.
 252. Wecksler, W. R., W. H. Okamura, and A. W. Norman. Studies on the mode of action of vitamin D. XIV. Quantitative assessment of the structural requirements for the interaction of 1α,25‐dihydroxyvitamin D3 with its chick intestinal mucosa receptor system. J. Steroid Biochem. 9: 929–937, 1978.
 253. Wiesner, R. H., R. Kumar, E. Seeman, and V. L. W. Go. Enterohepatic physiology of 1,25‐dihydroxyvitamin D3 metabolites in normal man. J. Lab. Clin. Med. 96: 1094–1100, 1980.
 254. Wilson, P. W., and D. E. M. Lawson. 1,25‐Dihydroxyvitamin D stimulation of specific membrane proteins in chick intestine. Biochim. Biophys. Acta 497: 805–811, 1977.
 255. Wilson, P. W. and D. E. M. Lawson. Incorporation of 3H‐leucine into an actin‐like protein in response to 1,25(OH)2D3 in chick intestinal brush borders. Biochem. J. 173: 627–631, 1978.
 256. Wilson, P. W., and D. E. M. Lawson. Vitamin D–dependent phosphorylation of an intestinal protein. Nature 289: 600–602, 1981.
 257. Windaus, A., F. Schenck, and F. von Weder. Über das antirachitisch wirksame bestrahlungs‐produkt aus 7‐dehydro‐cholesterin. Hoppe‐Seylers Z. Physiol. Chem. 241: 100–103, 1936.
 258. Yamamoto, M., Y. Kawanobe, H. Takahashi, E. Shimazawa, S. Kumura, and E. Ogata. Vitamin D deficiency and renal calcium transport in the rat. J. Clin. Invest. 74: 507–513, 1984.
 259. Yamaoki, K., Y. Seino, M. Ishida, T. Ishii, J. Shimotsuji, Y. Tanaka, H. Kurose, S. Matsuda, K. Satomura, and H. Yabuuchitt. Effect of dibutryl adenosine 3',5'‐monophosphate administration on plasma concentrations of 1,25‐dihydroxyvitamin D in pseudohypoparathyroidism type I. J. Clin. Endocrinol. Metab. 53: 1096–1100, 1981.
 260. Yoon, P. S., and H. F. DeLuca. Purification and properties of chick renal mitochondrial ferredoxin. Biochemistry 19: 2165–2171, 1980.
 261. Yoon, P. S., and H. F. DeLuca. Resolution and reconstitution of soluble components of rat liver microsomal vitamin D3‐25‐hydroxylase. Arch. Biochem. Biophys. 203: 529–541, 1980.
 262. Yoon, P. S., J. Rawlings, W. H. Orme‐Johnson, and H. F. DeLuca. Renal mitochondrial ferredoxin active in 25‐hydroxyvitamin D3‐1α‐hydroxylase. Characterization of the iron–sulfur cluster using interprotein cluster transfer and electron paramagnetic resonance spectroscopy. Biochemistry 19: 2172–2176, 1980.
 263. Zerwekh, J. E., M. R. Haussler, and T. J. Lindell. Rapid enhancement of chick intestinal DNA‐dependent RNA polymerase II activity by 1α,25‐dihydroxyvitamin D3 in vivo. Proc. Natl. Acad. Sci. USA 71: 2337–2341, 1974.
 264. Zerwekh, J. E., T. J. Lindell, and M. R. Haussler. Increased intestinal chromatin template activity: influence of 1α,25‐dihydroxyvitamin D3 and hormone–receptor complexes. J. Biol. Chem. 251: 2388–2394, 1976.

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Myron Gross, Rajiv Kumar. Vitamin D Endocrine System and Calcium and Phosphorus Homeostasis. Compr Physiol 2011, Supplement 25: Handbook of Physiology, Renal Physiology: 1817-1839. First published in print 1992. doi: 10.1002/cphy.cp080238