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Hypothalamohypophysiotropic Peptide Systems

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Abstract

The sections in this article are:

1 Anatomy of Hypothalamohypophysial System
1.1 Pituitary Gland
1.2 Hypophysial Portal Circulation
1.3 Hypothalamus
1.4 Anatomical Distribution of Releasing Factors in Hypothalamus
1.5 Aminergic Innervation of Hypothalamus
2 Biosynthesis, Storage, and Release of Hypothalamic Peptides
2.1 Biosynthesis of Hypothalamic Peptides
2.2 Peptide Storage
2.3 Peptide Release
3 Actions of Hypothalamic Hormones on Anterior Pituitary
3.1 Thyrotropin‐Releasing Hormone
3.2 Gonadotropin‐Releasing Hormone
3.3 Somatostatin
3.4 Corticotropin‐Releasing Hormone
3.5 Growth Hormone‐Releasing Factor
4 Central Nervous System Influences on Anterior Pituitary Regulation
4.1 Growth Hormone
4.2 Prolactin
4.3 Thyrotropin
4.4 Gonadotropins
4.5 Adrenocorticotropin and β‐Endorphin
5 Conclusions
Figure 1. Figure 1.

Structures of thyrotropin‐releasing hormone (TRH), gonadotropin‐releasing hormone (GnRH), somatostatin‐14, and ovine corticotropin‐releasing hormone (CRH).

Adapted from Martin et al. 240
Figure 2. Figure 2.

Schematic representation of hypothalamic regulation of pituitary gland. Left: hypothalamoneurohypophysial system; right: hypothalamoadenohypophysial system. Monoaminergic neurons on right form synapses on cell body and terminal of a tuberoinfundibular neuron. They represent CNS neurotransmitter regulation of anterior pituitary hormone release. Axoaxonic synapses as depicted are rare in median eminence, but aminergic terminals are frequent in contact zone of infundibulum and are in a position to release their transmitter close to terminals of tuberoinfundibular peptidergic neurons.

From Martin et al. 240
Figure 3. Figure 3.

Sagittal section of human pituitary and its stalk. A: blood supply; B: anatomical subdivisions of hypophysis. AT, artery of trabecula; IHA, inferior hypophysial artery; IP, infundibular process (posterior lobe); LIS, lower infundibular stem; LPV, long portal veins; PD, pars distalis (anterior lobe); PT, pars tuberalis; SHA, superior hypophysial artery; SPV, short portal veins; UIS, upper infundibular stem; V, venous sinus.

From Daniel and Pritchard 97
Figure 4. Figure 4.

Midsagittal sections of hypothalamus and pituitary of several species: A, human being; B, cat; C, sheep; D, ferret; E, rat. Anterior is at right, AC, anterior commissure; F, anterior column of fornix; IP, infundibular process (posterior lobe); IR, infundibular recess of third ventricle; LIS, lower infundibular stem; MB, mammillary body; ME, median eminence; MI, massa intermedia of thalamus; OC, optic chiasm; PD, pars distalis (anterior lobe); PI, pars intermedia (intermediate lobe); S, pituitary stalk; SR, supraoptic recess of third ventricle. Note that human being lacks a well‐demarcated median eminence.

From Daniel and Pritchard 97
Figure 5. Figure 5.

Vascular cast of pituitary stalk of monkey in midsagittal section. One of paired superior hypophysial arteries is indicated by arrowhead. This vessel supplies both medial basal hypothalamus (HYP) and pituitary stalk‐median eminence. A dense capillary plexus in the stalk‐median eminence takes various shapes (A, B, C, D). These capillaries drain into relatively larger portal vessels, which pass down to pars distalis (PD) and again divide into capillaries and venous sinuses.

From Page et al. 283
Figure 6. Figure 6.

Major nuclei of human hypothalamus. Nucleus infundibularis corresponds to arcuate nucleus. Upper figure shows lateral hypothalamus; lower figure shows medial hypothalamus.

From color illustration of Nauta and Haymaker 268. In: The Hypothalamus, © 1969. Courtesy of Charles C Thomas, Publisher, Springfield, Illinois
Figure 7. Figure 7.

Electron micrograph of nerve terminals in external lamina of rat median eminence. A, axon terminal; BM, basement membrane of capillary endothelium; DCV, dense‐core vesicles; G, glial (tanycyte) process; PS, perivascular space; SV, synaptic vesicles.

From Knigge and Scott 207
Figure 8. Figure 8.

Distribution of TRH immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Darker cross hatching and stippling denote greater concentration. A: parasagittal section; B, C, D: coronal sections, anterior to posterior, a, Nucleus accumbens; C, caudate; CA, anterior commissure; cc, corpus callosum; F, fornix; M, mesencephalon; MB, mammillary body; ME, median eminence; MFB, medial forebrain bundle; MT, mammillothalamic tract; NA, arcuate nucleus; NDM, dorsomedial nucleus; NHA, anterior hypothalamic nucleus; NHP, posterior hypothalamic nucleus; NIST, interstitial nucleus of stria terminalis; NPE, periventricular nucleus; NPF, perifornical nucleus; NPMD, dorsal premammillary nucleus; NPMV, ventral premammillary nucleus; NPOm, medial preoptic nucleus; NPV, paraventricular nucleus; NSC, suprachiasmatic nucleus; NSO, supraoptic nucleus; NVM, ventromedial nucleus; NVM1, ventromedial nucleus, lateral division; NVMM, ventromedial nucleus, medial division; OC, optic chiasm; P, pituitary; RE, nucleus reuniens thalami; S, preoptic suprachiasmatic nucleus; Sd, dorsal septal nucleus; Si, intermediate septal nucleus; Sl, lateral septal nucleus, Sm, medial septal nucleus; SM, stria medullaris; td, nucleus of diagonal band; TH, thalamus; ZI, zona incerta.

From Brownstein et al. 64. Copyright 1974 by the American Association for the Advancement of Science
Figure 9. Figure 9.

Distribution of GnRH immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Density of stippling indicates relative concentration of hormone. ar, Arcuate nucleus; CA, anterior commissure; CO, optic chiasm; ha, anterior hypothalamic nucleus; hdv, dorsomedial nucleus; hvm, ventromedial nucleus; MI, massa intermedia; OVLT, organum vasculosum of lamina terminalis; pom, medial preoptic nucleus; posc, suprachiasmatic preoptic nucleus; mmm, medial mammillary nucleus; sc, suprachiasmatic nucleus.

From McCann 244. Reprinted by permission of The New England Journal of Medicine.
Figure 10. Figure 10.

Distribution of somatostatin‐14‐like immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Abbreviations as in Fig. 8.

From Brownstein et al. 61, © 1975, The Endocrine Society
Figure 11. Figure 11.

Fluorescence immunocytochemistry of rat median eminence in coronal section. Asterisk denotes lumen of third ventricle. Antisera were directed against A, tyrosine hydroxylase; B, GnRH; C, TRH; and D, somatostatin. Note inhomogeneous distribution of immunoreactive terminals for tyrosine hydroxylase, GnRH, and TRH in external lamina of median eminence. Note also tyrosine hydroxylase–positive cell bodies in arcuate nucleus and dense meshwork of somatostatin‐containing fibers in same region.

From Hökfelt et al. 180
Figure 12. Figure 12.

Structure and posttranslational processing of arginine vasopressin preprohormone as predicted from cDNA nucleotide sequence and confirmed by amino acid analysis of posterior pituitary peptides. Circled C represents carbohydrate side chain in glycoprotein segment of molecule.

From Land et al. 219. Reprinted by permission from Nature, copyright 1982, Macmillan Journals Limited
Figure 13. Figure 13.

Gel permeation chromatogram of a pool of acetic acid extracts of rat hypothalami run on Bio Gel P‐30 column. Fractions were collected and assayed for somatostatin by radioimmunoassay. Ordinate is percent B/B0, a nonlinear measure of immunoreactivity. Peaks of higher apparent molecular weight than somatostatin‐14 are larger than appear on linear scale. Peak fractions of each reference substance run are marked by arrows. V0, dextran blue; Cyt c, cytochrome c (Mr 12,300).

From Sagar et al. 335


Figure 1.

Structures of thyrotropin‐releasing hormone (TRH), gonadotropin‐releasing hormone (GnRH), somatostatin‐14, and ovine corticotropin‐releasing hormone (CRH).

Adapted from Martin et al. 240


Figure 2.

Schematic representation of hypothalamic regulation of pituitary gland. Left: hypothalamoneurohypophysial system; right: hypothalamoadenohypophysial system. Monoaminergic neurons on right form synapses on cell body and terminal of a tuberoinfundibular neuron. They represent CNS neurotransmitter regulation of anterior pituitary hormone release. Axoaxonic synapses as depicted are rare in median eminence, but aminergic terminals are frequent in contact zone of infundibulum and are in a position to release their transmitter close to terminals of tuberoinfundibular peptidergic neurons.

From Martin et al. 240


Figure 3.

Sagittal section of human pituitary and its stalk. A: blood supply; B: anatomical subdivisions of hypophysis. AT, artery of trabecula; IHA, inferior hypophysial artery; IP, infundibular process (posterior lobe); LIS, lower infundibular stem; LPV, long portal veins; PD, pars distalis (anterior lobe); PT, pars tuberalis; SHA, superior hypophysial artery; SPV, short portal veins; UIS, upper infundibular stem; V, venous sinus.

From Daniel and Pritchard 97


Figure 4.

Midsagittal sections of hypothalamus and pituitary of several species: A, human being; B, cat; C, sheep; D, ferret; E, rat. Anterior is at right, AC, anterior commissure; F, anterior column of fornix; IP, infundibular process (posterior lobe); IR, infundibular recess of third ventricle; LIS, lower infundibular stem; MB, mammillary body; ME, median eminence; MI, massa intermedia of thalamus; OC, optic chiasm; PD, pars distalis (anterior lobe); PI, pars intermedia (intermediate lobe); S, pituitary stalk; SR, supraoptic recess of third ventricle. Note that human being lacks a well‐demarcated median eminence.

From Daniel and Pritchard 97


Figure 5.

Vascular cast of pituitary stalk of monkey in midsagittal section. One of paired superior hypophysial arteries is indicated by arrowhead. This vessel supplies both medial basal hypothalamus (HYP) and pituitary stalk‐median eminence. A dense capillary plexus in the stalk‐median eminence takes various shapes (A, B, C, D). These capillaries drain into relatively larger portal vessels, which pass down to pars distalis (PD) and again divide into capillaries and venous sinuses.

From Page et al. 283


Figure 6.

Major nuclei of human hypothalamus. Nucleus infundibularis corresponds to arcuate nucleus. Upper figure shows lateral hypothalamus; lower figure shows medial hypothalamus.

From color illustration of Nauta and Haymaker 268. In: The Hypothalamus, © 1969. Courtesy of Charles C Thomas, Publisher, Springfield, Illinois


Figure 7.

Electron micrograph of nerve terminals in external lamina of rat median eminence. A, axon terminal; BM, basement membrane of capillary endothelium; DCV, dense‐core vesicles; G, glial (tanycyte) process; PS, perivascular space; SV, synaptic vesicles.

From Knigge and Scott 207


Figure 8.

Distribution of TRH immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Darker cross hatching and stippling denote greater concentration. A: parasagittal section; B, C, D: coronal sections, anterior to posterior, a, Nucleus accumbens; C, caudate; CA, anterior commissure; cc, corpus callosum; F, fornix; M, mesencephalon; MB, mammillary body; ME, median eminence; MFB, medial forebrain bundle; MT, mammillothalamic tract; NA, arcuate nucleus; NDM, dorsomedial nucleus; NHA, anterior hypothalamic nucleus; NHP, posterior hypothalamic nucleus; NIST, interstitial nucleus of stria terminalis; NPE, periventricular nucleus; NPF, perifornical nucleus; NPMD, dorsal premammillary nucleus; NPMV, ventral premammillary nucleus; NPOm, medial preoptic nucleus; NPV, paraventricular nucleus; NSC, suprachiasmatic nucleus; NSO, supraoptic nucleus; NVM, ventromedial nucleus; NVM1, ventromedial nucleus, lateral division; NVMM, ventromedial nucleus, medial division; OC, optic chiasm; P, pituitary; RE, nucleus reuniens thalami; S, preoptic suprachiasmatic nucleus; Sd, dorsal septal nucleus; Si, intermediate septal nucleus; Sl, lateral septal nucleus, Sm, medial septal nucleus; SM, stria medullaris; td, nucleus of diagonal band; TH, thalamus; ZI, zona incerta.

From Brownstein et al. 64. Copyright 1974 by the American Association for the Advancement of Science


Figure 9.

Distribution of GnRH immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Density of stippling indicates relative concentration of hormone. ar, Arcuate nucleus; CA, anterior commissure; CO, optic chiasm; ha, anterior hypothalamic nucleus; hdv, dorsomedial nucleus; hvm, ventromedial nucleus; MI, massa intermedia; OVLT, organum vasculosum of lamina terminalis; pom, medial preoptic nucleus; posc, suprachiasmatic preoptic nucleus; mmm, medial mammillary nucleus; sc, suprachiasmatic nucleus.

From McCann 244. Reprinted by permission of The New England Journal of Medicine.


Figure 10.

Distribution of somatostatin‐14‐like immunoreactivity within rat hypothalamus as determined by microdissection and radioimmunoassay. Abbreviations as in Fig. 8.

From Brownstein et al. 61, © 1975, The Endocrine Society


Figure 11.

Fluorescence immunocytochemistry of rat median eminence in coronal section. Asterisk denotes lumen of third ventricle. Antisera were directed against A, tyrosine hydroxylase; B, GnRH; C, TRH; and D, somatostatin. Note inhomogeneous distribution of immunoreactive terminals for tyrosine hydroxylase, GnRH, and TRH in external lamina of median eminence. Note also tyrosine hydroxylase–positive cell bodies in arcuate nucleus and dense meshwork of somatostatin‐containing fibers in same region.

From Hökfelt et al. 180


Figure 12.

Structure and posttranslational processing of arginine vasopressin preprohormone as predicted from cDNA nucleotide sequence and confirmed by amino acid analysis of posterior pituitary peptides. Circled C represents carbohydrate side chain in glycoprotein segment of molecule.

From Land et al. 219. Reprinted by permission from Nature, copyright 1982, Macmillan Journals Limited


Figure 13.

Gel permeation chromatogram of a pool of acetic acid extracts of rat hypothalami run on Bio Gel P‐30 column. Fractions were collected and assayed for somatostatin by radioimmunoassay. Ordinate is percent B/B0, a nonlinear measure of immunoreactivity. Peaks of higher apparent molecular weight than somatostatin‐14 are larger than appear on linear scale. Peak fractions of each reference substance run are marked by arrows. V0, dextran blue; Cyt c, cytochrome c (Mr 12,300).

From Sagar et al. 335
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Stephen M. Sagar, Joseph B. Martin. Hypothalamohypophysiotropic Peptide Systems. Compr Physiol 2011, Supplement 4: Handbook of Physiology, The Nervous System, Intrinsic Regulatory Systems of the Brain: 413-462. First published in print 1986. doi: 10.1002/cphy.cp010408