Endocrinology, lecture on Neurohypophysis
XII. Neurohypophysial Nonapeptides
A. cysteine-cysteine disulfide bonds
1. hid # of amino acids - thought of as octapeptides for many years
B. Arginine Vasopressin (AVP, aka ADH)
1. NH2 - Cys - Tyr- Phe - Gln - Asn - Cys - Pro - Arg - Gly - COOH
|_____S_____S________|
C. Oxytocin (OT, OxT, Oxy)
1. NH2 - Cys - Tyr- Ile - Gln - Asn - Cys - Pro - Leu - Gly - COOH
|_____S_____S_______|
D. Arginine Vasotocin (AVT)
1. NH2 - Cys - Tyr- Ile - Gln - Asn - Cys - Pro - Arg - Gly - COOH
|_____S_____S_______|
E. Synthesized by the SON and PVN of the hypothalamus (neurosecretory neurons)
1. supraoptic nucleus mostly AVP æ
magnocellular subnuclei
2. paraventricular nucleus mostly OT ä
3. secreted by neurohypophysis into capillary of
inferior hypophysial vasculature
a. neurohemal organ
b. depolarization of neurosecretory neurons
causes release of AVP or OT
c. some AVP fibers terminate in the median eminence,
contact hypophysial portal capillaries
i. AVP enhances CRH stimulation of ACTH
ii. AVP + CRH colocalized in PVN neuron terminals
d. AVP & OT fibers project into the brain and spinal cord
i. act as neurotransmitters or neuromodulators
ii. regulate autonomic nervous system (PVN)
4. produced in golgi along with neurophysins
a. neurophysins bind as carrier proteins specifically with AVP or OT
i. neurophysin I for OT
ii. neurophysin II for AVP
C. Receptors
1. AVP
a. membrane receptors in kidney, liver, pituitary, blood vessels,
platelets, testes, and some tumors
b. Kd ~ 1nM ([hormonal] 1/2-max R occupancy)
i. ED50 is lower ([hormonal] 1/2-maximal response)
c. two types V1 and V2
i. V1 in liver, blood vessels and all extrarenal sites
(1) IP3, DG, Ca++/Calmodulin
ii. V2 only in renal tubules
(1) AC, cAMP
2. OT
a. one type receptor functionally homologous to V1 receptors
i. contraction of smooth muscle
b. IP3, DG, Ca++/Calmodulin
i. Ca++ release is central to all muscle contraction
including smooth muscle
c. OT receptors found in the smooth muscle of the
uterus, vas deferens, and mammary
D. Physiological Actions
1. AVP
a. Osmoregulation
i. AVP affects collecting duct and ascending loop of Henle
in the nephron, and the afferent and efferent arterioles
(1) V2 receptors only on tubules
ii. osmotic permeability of renal tubules is increased
(1) water is reabsorbed - antidiuresis
iii. AVP release controlled by osmoreceptors in the brain
(1) regulates positively and negatively around
critical value of blood osmotic pressure
(2) highly sensitive
(3) no habituation
iv. no direct effect on filtration rate or
elimination of solutes from kidney
b. Blood pressure
i. ñ via V1 receptors contracting
smooth muscle of arterioles
ii. along with Sympathetic NE/Epi
and the Renin-Angiotensin System
(evaluating the contribution of each difficult)
(1) ñ efficiency of reflex regulation
of BP by Autonomic NS
iii. ¯ cardiac output
iv. ñ dipsogenesis - drinking
c. control of ACTH secretion
i. potentiates CRH
ii. colocalization in neurosecretory neurons
that terminate on the median eminence
(1) not effected by osmotic pressure
2. OT
a. Milk Ejection Reflex
i. OT stimulated by suction on the nipple
ii. neuroendocrine reflex
b. Uterine contraction/Parturition (also a neuroendocrine reflex)
i. Oxytocin receptors increase before OT during labor
(1) labor begins
(2) increased neural feedback from
the cervix and uterus ® ñ OT
ii. OT directly causes contraction of uterine myometrium
iii. also mediated by release of the paracrine PGF2a
c. Orgasm
i. smooth muscle contraction in vas deferens
and ducts of the vestibular glands
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