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Antidiuretic Hormone: Synthesis and Release

Celia D. Sladek

10.1002/cphy.cp070312

Source: Supplement 22: Handbook of Physiology, The Endocrine System, Endocrine Regulation of Water and Electrolyte Balance

Originally published: 2000

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Morphology of Vasopressinergic Neurons
1.1 Localization
1.2 Cellular Morphology
1.3 Glial–Neuronal Interactions
1.4 Posterior Pituitary Morphology
2 Synthesis of Vasopressin
2.1 Vasopressin Gene
2.2 Regulation of Vasopressin mRNA
2.3 Processing, Packaging, and Transport to the Neural Lobe
3 Release of Antidiuretic Hormone
3.1 Electrophysiological Characteristics of Vasopressin Neurons
3.2 Stimulus–Secretion Coupling in the Neural Lobe
3.3 Dendritic Release
4 Regulation of Vasopressin Secretion
4.1 Afferents to Magnocellular Vasopressin Neurons
4.2 Neurochemicals Regulating Secretion
4.3 Neuropeptides in Afferent Pathways
4.4 Osmoregulatory Pathways and Mechanisms
4.5 Pressure/Volume‐Regulatory Pathways
4.6 Other Ascending Pathways
4.7 Other Physiological Regulators
4.8 Steroid hormones
Figure 1. Figure 1.

Vasopressin and oxytocin neurons of the neurohypophyseal system as visualized by immunohistochemical staining for associated neurophysins. Dense staining is seen within neurons of the paraventricular (PVN) and supraoptic (SON) nuclei. Axons from the PVN (arrows) extend laterally and ventrally to join axons emanating from the SON to form the hypothalamo‐neurohypophyseal tract. Stained neurons belonging to accessory nuclei are seen in the path of axons from the PVN. Smaller stained neurons are also seen in the suprachiasmatic nucleus (SCN); however, this nucleus does not contribute fibers to the neural lobe. OC, optic chiasm; V, third ventricle. [From Sladek and Sladek 524 with permission.]
Figure 2. Figure 2.

Schematic representation of VP and oxytocin genes, mRNA transcripts, precursors, and final protein products. [From Swenson 551 with permission; (Compiled from refs. 85, 362, 364, 365, 450]. GRE, glucocorticoid‐response element; AP2, activator protein‐2; CRE, cAMP‐response element; VP, vasopressin; OT, oxytocin; RAR, retinoic acid receptor;
Figure 3. Figure 3.

Characteristic firing patterns for VP neurons (A) and oxytocin neurons (B) recorded from an anesthetized female rat during suckling. Blood pressure, unit activity (each pen deflection = 1 spike), intramammary pressure, and firing rate are plotted. Milk ejections (m.e) are indicated, and in (B), but not (A), each milk ejection is preceded by a burst of high‐frequency firing (filled arrows). Blood withdrawal elicited increased firing rate in both A and B; in A, following a period of continuous high‐frequency firing, a phasic firing pattern was established, whereas in B continuous high‐frequency firing was maintained throughout the period of hypovolemia. Following blood return, the cell in B continued to fire, whereas the cell in A was inhibited. [From Poulain et al. 430 with permission.]
Figure 4. Figure 4.

A: Depolarizing afterpotential (DAP) and resulting plateau potential (P) recorded in a phasically firing neuron. A DAP followed each action potential during the period between bursts. Summation of DAPs led to P and a burst of firing. [From Andrew and Dudek 16 with permission.] B: Frequency dependence of the after‐hyperpolarization (A.h.p.). At low frequency (10 Hz), a plateau potential (P) followed the spike train, but at higher frequencies the spike train was followed by the after‐hyperpolarization. [From Andrew and Dudek 18 with permission.] C: Spike broadening. Left panel: Superimposed recordings of consecutive action potentials recorded from magnocellular neurons during a current‐evoked train. Spikes broaden progressively and then maintain a longer duration. Right panel: Effect of frequency on spike duration in magnocellular neurons. Action potentials recorded at four different firing rates. [From Bourque and Renaud 71 with permission.]
Figure 5. Figure 5.

Ultrastructural evidence of exocytosis in neurohypophyseal nerve terminals from water‐deprived rats. A: The contents of a neurosecretory granule (nsg) are localized to the extracellular space (arrow) as a result of fusion of granule membrane with plasma membrane during exocytosis. × 70,000. B, C: Scanning electron micrographs of neurosecretory granule core material (core) localized in the extracellular space (B) and exiting the neurosecretory granule (C). × 92,000. [From Theodosis et al. 559 with permission.]
Figure 6. Figure 6.

Innervation of the supraoptic nucleus (SON) and adjacent perinuclear zone (PNZ). Important features to note are as follows: (1) afferent connections of the SON are shown because, unlike the paraventricular nucleus (PVN), the SON is comprised almost entirely of magnocellular neurons projecting to the neural lobe; (2) several CNS areas terminate in the area adjacent to the nucleus, possibly reflecting terminals on vasopressin (VP) or oxytocin (OT) proximal dendrites or innervation of other neurons in this area [for example, cholinergic (Ach), glutamatergic (Glu), γ‐aminobutyric acid (GABA), somatostatin (SRIF)], which in turn project to the SON proper; (3) relatively few of the inputs are confined to either the VP or oxytocin neurons, but it does appear that β‐endorphin (β‐endo), serotonin (5‐HT), and the somatostatin (SRIF)/inhibin projections may be selective for oxytocin neurons, whereas the norepinephrine (NE)/neuropeptide Y (NPY)/ATP projection is densest in the ventral, VP‐rich portion of the nucleus and in the ventral dendritic zone; (4) transmitters have not been identified for some of the inputs. AII, angiotensin II; ANP, atrial natriuretic peptide; AVPV, anteroventral periventricular region; AV3V, anterior ventral third ventricle; DA, dopamine; EAA, excitatory amino acid; Hist, histamine; MPO, median preoptic nucleus; OC, optic chiasm; OVLT, organum vasculosum of the lamina terminalis; PBN, parabrachial nucleus; SFO, subfornical organ; SP, substance P; TM, tuberomamillary nucleus. [Revised from Sladek and Armstrong 513 with permission.]
Figure 7. Figure 7.

Innervation of the neural lobe. In addition to the VP and oxytocin nerve terminals, the neural lobe contains a variety of other peptides and transmitters that are either co‐localized in the VP and oxytocin terminals or localized in fine fibers innervating the neural lobe. Most of these fine fibers arise from periventricular structures. *Other substances co‐localized in VP neurons include prolactin‐like peptides, 7B2, neuropeptide FF, VGF, T‐kininogen, and probably endothelin, dopamine (DA), and nitric oxide (NO) (see text); other peptides co‐localized in oxytocin neurons include endothelin and NO, and expression of galanin, thyrotropin‐releasing hormone, dynorphin, and enkephalin can be induced by hypophysectomy or dehydration. The importance of these agents in regulating VP release remains to be determined (see text). The presence of synthetic enzymes, tyrosine hydroxylase (TH) and nitric oxide synthase (NOS), in VP and oxytocin neurons suggests that dopamine and NO may be produced in these cells and, therefore, released from the neural lobe. 5HT, serotonin; CCK, cholecystokinin; CRH, corticotropin‐releasing hormone; NPY, neuropeptide Y; OC, optic chiasm; OT, oxytocin; SRIF, somatostatin; VP, vasopressin; AII, angiotensin II; GABA, γ‐aminobutyric acid; NT, neurotensin. [Revised from Sladek and Armstrong 513 with permission.]


Figure 1.

Vasopressin and oxytocin neurons of the neurohypophyseal system as visualized by immunohistochemical staining for associated neurophysins. Dense staining is seen within neurons of the paraventricular (PVN) and supraoptic (SON) nuclei. Axons from the PVN (arrows) extend laterally and ventrally to join axons emanating from the SON to form the hypothalamo‐neurohypophyseal tract. Stained neurons belonging to accessory nuclei are seen in the path of axons from the PVN. Smaller stained neurons are also seen in the suprachiasmatic nucleus (SCN); however, this nucleus does not contribute fibers to the neural lobe. OC, optic chiasm; V, third ventricle. [From Sladek and Sladek 524 with permission.]



Figure 2.

Schematic representation of VP and oxytocin genes, mRNA transcripts, precursors, and final protein products. [From Swenson 551 with permission; (Compiled from refs. 85, 362, 364, 365, 450]. GRE, glucocorticoid‐response element; AP2, activator protein‐2; CRE, cAMP‐response element; VP, vasopressin; OT, oxytocin; RAR, retinoic acid receptor;



Figure 3.

Characteristic firing patterns for VP neurons (A) and oxytocin neurons (B) recorded from an anesthetized female rat during suckling. Blood pressure, unit activity (each pen deflection = 1 spike), intramammary pressure, and firing rate are plotted. Milk ejections (m.e) are indicated, and in (B), but not (A), each milk ejection is preceded by a burst of high‐frequency firing (filled arrows). Blood withdrawal elicited increased firing rate in both A and B; in A, following a period of continuous high‐frequency firing, a phasic firing pattern was established, whereas in B continuous high‐frequency firing was maintained throughout the period of hypovolemia. Following blood return, the cell in B continued to fire, whereas the cell in A was inhibited. [From Poulain et al. 430 with permission.]



Figure 4.

A: Depolarizing afterpotential (DAP) and resulting plateau potential (P) recorded in a phasically firing neuron. A DAP followed each action potential during the period between bursts. Summation of DAPs led to P and a burst of firing. [From Andrew and Dudek 16 with permission.] B: Frequency dependence of the after‐hyperpolarization (A.h.p.). At low frequency (10 Hz), a plateau potential (P) followed the spike train, but at higher frequencies the spike train was followed by the after‐hyperpolarization. [From Andrew and Dudek 18 with permission.] C: Spike broadening. Left panel: Superimposed recordings of consecutive action potentials recorded from magnocellular neurons during a current‐evoked train. Spikes broaden progressively and then maintain a longer duration. Right panel: Effect of frequency on spike duration in magnocellular neurons. Action potentials recorded at four different firing rates. [From Bourque and Renaud 71 with permission.]



Figure 5.

Ultrastructural evidence of exocytosis in neurohypophyseal nerve terminals from water‐deprived rats. A: The contents of a neurosecretory granule (nsg) are localized to the extracellular space (arrow) as a result of fusion of granule membrane with plasma membrane during exocytosis. × 70,000. B, C: Scanning electron micrographs of neurosecretory granule core material (core) localized in the extracellular space (B) and exiting the neurosecretory granule (C). × 92,000. [From Theodosis et al. 559 with permission.]



Figure 6.

Innervation of the supraoptic nucleus (SON) and adjacent perinuclear zone (PNZ). Important features to note are as follows: (1) afferent connections of the SON are shown because, unlike the paraventricular nucleus (PVN), the SON is comprised almost entirely of magnocellular neurons projecting to the neural lobe; (2) several CNS areas terminate in the area adjacent to the nucleus, possibly reflecting terminals on vasopressin (VP) or oxytocin (OT) proximal dendrites or innervation of other neurons in this area [for example, cholinergic (Ach), glutamatergic (Glu), γ‐aminobutyric acid (GABA), somatostatin (SRIF)], which in turn project to the SON proper; (3) relatively few of the inputs are confined to either the VP or oxytocin neurons, but it does appear that β‐endorphin (β‐endo), serotonin (5‐HT), and the somatostatin (SRIF)/inhibin projections may be selective for oxytocin neurons, whereas the norepinephrine (NE)/neuropeptide Y (NPY)/ATP projection is densest in the ventral, VP‐rich portion of the nucleus and in the ventral dendritic zone; (4) transmitters have not been identified for some of the inputs. AII, angiotensin II; ANP, atrial natriuretic peptide; AVPV, anteroventral periventricular region; AV3V, anterior ventral third ventricle; DA, dopamine; EAA, excitatory amino acid; Hist, histamine; MPO, median preoptic nucleus; OC, optic chiasm; OVLT, organum vasculosum of the lamina terminalis; PBN, parabrachial nucleus; SFO, subfornical organ; SP, substance P; TM, tuberomamillary nucleus. [Revised from Sladek and Armstrong 513 with permission.]



Figure 7.

Innervation of the neural lobe. In addition to the VP and oxytocin nerve terminals, the neural lobe contains a variety of other peptides and transmitters that are either co‐localized in the VP and oxytocin terminals or localized in fine fibers innervating the neural lobe. Most of these fine fibers arise from periventricular structures. *Other substances co‐localized in VP neurons include prolactin‐like peptides, 7B2, neuropeptide FF, VGF, T‐kininogen, and probably endothelin, dopamine (DA), and nitric oxide (NO) (see text); other peptides co‐localized in oxytocin neurons include endothelin and NO, and expression of galanin, thyrotropin‐releasing hormone, dynorphin, and enkephalin can be induced by hypophysectomy or dehydration. The importance of these agents in regulating VP release remains to be determined (see text). The presence of synthetic enzymes, tyrosine hydroxylase (TH) and nitric oxide synthase (NOS), in VP and oxytocin neurons suggests that dopamine and NO may be produced in these cells and, therefore, released from the neural lobe. 5HT, serotonin; CCK, cholecystokinin; CRH, corticotropin‐releasing hormone; NPY, neuropeptide Y; OC, optic chiasm; OT, oxytocin; SRIF, somatostatin; VP, vasopressin; AII, angiotensin II; GABA, γ‐aminobutyric acid; NT, neurotensin. [Revised from Sladek and Armstrong 513 with permission.]

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Article Title: Antidiuretic Hormone: Synthesis and Release
 

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Celia D. Sladek. Antidiuretic Hormone: Synthesis and Release. Compr Physiol 2011, Supplement 22: Handbook of Physiology, The Endocrine System, Endocrine Regulation of Water and Electrolyte Balance: 436-495. First published in print 2000. doi: 10.1002/cphy.cp070312