Endocrinology, lecture on Neurohypophysis
USD Department of Biology
Endocrinology
Summers
Hormones
Endocrine Glands
Receptors
Homeostasis
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Steroids
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Prolactin
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
GI Hormones
Guts 'n Brains
Brain Hormones
Neurosteroids
Neuropeptides
Endocrine Evolution
Figures for Endocrionology
text:Vertebrate Endocrinology5th Edition - David O. Norris and James A. Carr:
Read pages 217-225 for this lecture
acronyms    end
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.  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)  efficiency of reflex regulation
					      of BP by Autonomic NS


				iii. ¯ cardiac output


				iv.  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 ®  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

XIII. Thyroid Axis

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