Pituitary (AP + PP) 09 and Pineal Glands • � Introduction to hypothalamus, pituitary and pineal function. • � Posterior pituitary hormones (OT, AVP) and their secretion, function and regulation. Countercurrent mechanism and the effect of AVP on collecting ducts. Mechanism of action and control of AVP secretion: osmotic stimulation, baroregulation, additional cellular actions. AVP pathologies: hypothalamic / nephrogenic diabetes insipidus (DI), SIADH, gene mutation in familial DI. • � Anterior pituitary melanotropic hormones (ßEND, MSH) and their secretion, function and regulation. MSH effects on pigmentation and food intake, species variability, regulation, rhytms, receptors, mechanism of action. ßEND central and peripheral effects, action mechanism. • � Pineal hormones (melatonin) and their secretion, function and regulation. Melatonin: biosynthesis, N-acetyl transferase activity and rhytms, light - dark cycle, physiological functions, sleep, behavioral rhythmicity, reproduction, thermoregulation. Introduction Hormones and “story lines” Components of a hormone response system. Responses produced by hormones generally are sensed by whatever apparatus activated the secretion and usually decrease further secretion. Page 1
Introduction Hormones and “story lines” Components of a hormone response system. Responses produced by hormones generally are sensed by whatever apparatus activated the secretion and usually decrease further secretion. Posterior Pituitary Hormones PVN, SON, • � Hypothalamic hypophyseal connection tract Posterior • � Oxytocin pituitary (OT) AVP = ADH • � Vasopressin OT (AVP, ADH) • � AVP, blood pressure and water control Page 2
Posterior Pituitary Hormones • � Hypothalamic thirst, Na appetite connection maternal behavior • � Oxytocin (OT) � � POA PVN • � Vasopressin S E SON (AVP, ADH) ME S • � AVP, blood hepatic portal vein pressure and natriuresis / antidiuresis osmoreceptors water control mechanoreceptors uterine contraction E in cervix and breast and milk ejection � Inputs and outputs to hypothalamic S E integration centers ( � ) like PVN, SON Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control � Peripheral info reaches brain integration S E centers through nervous system Page 3
Posterior Pituitary Hormones • � Hypothalamic connection peripheral afferent • � Oxytocin information (OT) also reaches brain integration centers • � Vasopressin (AVP, ADH) through the vascular system • � AVP, blood (e.g. to osmo- pressure and receptors) water control � S E Posterior Pituitary Hormones • � Hypothalamic 1 - 9 109 - 147 connection N H COOH 2 neurophysin II • � Oxytocin - Gly glycoprotein (OT) ADH AVP -----> • � Vasopressin 1 - 9 105 - 106 (AVP, ADH) N H - - COOH 2 neurophysin I • � AVP, blood pressure and - Gly water control OT -----> His � AVP / OT are nonapeptides with disulfide bond between cystine residues 1 - 6. Precursors, S E encoded by distinct but structurally related genes, are processed on route to PP Page 4
Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control � AVP / OT are nonapeptides with disulfide bond between cystine residues 1 - 6. Precursors, S E encoded by distinct but structurally related genes, are processed on route to PP Posterior Pituitary Hormones • � Hypothalamic connection Milk release Uterine contraction • � Oxytocin (OT) Vascular smooth muscle • � Vasopressin Anterior pituitary (AVP, ADH) Maternal behavior • � AVP, blood Sexual behavior pressure and water control Feeding behavior � S E (additional information in the reproduction lectures) Page 5
Posterior Pituitary Hormones • � Hypothalamic connection Milk release Uterine contraction • � Oxytocin (OT) Vascular smooth muscle • � Vasopressin Anterior pituitary (AVP, ADH) Maternal behavior • � AVP, blood Positive feedback regulation of oxytocin secretion. Sexual behavior pressure and (1) Uterine contractions at the onset of parturition apply mild stretch to the cervix. (2) In response to water control sensory input from the cervix (blue arrows), oxytocin is secreted from the posterior pituitary gland, and stimulates (green arrows) further Feeding behavior contraction of the uterus, which, in turn stimulates � secretion of more oxytocin (3) leading to further stretching of the cervix, and even more oxytocin secretion (4), until the fetus is expelled (5). S E (additional information in the reproduction lectures) Posterior Pituitary Hormones • � Hypothalamic connection Milk release Uterine contraction • � Oxytocin (OT) Vascular smooth muscle • � Vasopressin Anterior pituitary (AVP, ADH) Maternal behavior • � AVP, blood Sexual behavior pressure and water control Feeding behavior � S E (additional information in the reproduction lectures) Page 6
Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control � Regulation of vasopressin secretion. Increased blood osmolality or decreased blood volume are S E sensed in the brain or thorax, respectively, and increase vasopressin secretion. Vasopressin, acting principally on the kidney, produces changes that restore osmolality and volume, thereby shutting down further secretion in a negative feedback arrangement. Further details are given in Chapter 9. Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control � Structures of the hormones of the neurohypophysis and their prohormone precursors. Because final processing of the prohormones takes place in the secretory granules, the neurophysins and the glycopeptide fragment are cosecreted with oxytocin or vasopressin, but S E have no known physiological actions. Amino acid sequences of oxytocin and vasopressin are shown in the single letter code: C = cysteine, Y = tyrosine, F = phenylalanine, I = isoleucine, Q = glutamine, N = asparagine. P = proline, R = arginine, L = leucine, G = glycine. Page 7
Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control � Desmopressin is a synthetic analog of vassopresin S E Posterior Pituitary Hormones • � Hypothalamic connection • � Oxytocin (OT) • � Vasopressin (AVP, ADH) • � AVP, blood pressure and water control AVP gene also code for its carrier � neurophysin S E Page 8
Posterior Pituitary Hormones • � Hypothalamic connection • � kidney, nephron, medulla • � counter- • � Oxytocin current (OT) mechanism • � descending, ascending • � Vasopressin loop of Henle (AVP, ADH) • � gradient, diuretics AVP / ADH effect • � AVP, blood • � AQP (1-4) pressure and water control AVP main effect is antidiuresis but the � “driving force” is the kidney medullary S E countercurrent mechanism Posterior Pituitary Hormones • � Hypothalamic connection • � kidney, nephron, medulla • � counter- • � Oxytocin current (OT) mechanism • � descending, ascending • � Vasopressin loop of Henle (AVP, ADH) • � gradient, diuretics AVP / ADH effect • � AVP, blood • � AQP (1-4) pressure and water control AVP main effect is antidiuresis but the � “driving force” is the kidney medullary S E countercurrent mechanism Page 9
Posterior Pituitary Hormones • � Hypothalamic connection • � kidney, nephron, medulla • � counter- • � Oxytocin current (OT) mechanism • � descending, ascending • � Vasopressin loop of Henle (AVP, ADH) • � gradient, diuretics AVP / ADH effect • � AVP, blood • � AQP (1-4) pressure and water control AVP main effect is antidiuresis but the � “driving force” is the kidney medullary S E countercurrent mechanism Posterior Pituitary Hormones • � Hypothalamic connection • � kidney, AVP-V2 nephron, receptor medulla • � counter- • � Oxytocin current (OT) mechanism • � descending, ascending • � Vasopressin loop of Henle (AVP, ADH) • � gradient, diuretics AVP / ADH effect • � AVP, blood • � AQP (1-4) pressure and water control ADH receptors have 7- tm domains characteristic of � GPCR: V1a (hepatic) and V1b (AP) act through IP3 to mobilize Ca; the V2r (kidney) coupled to AC (V2r, Gs, S E AC, cAMP, PKA, AQP2)has 48% homology with OTr; V3 is expressed in AP Page 10
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