Neurohypophysis

1
Neurohypophysis

• Products oxytocin, vasopressin
• Cell bodies of neurosecretory neurons exist in
  SON, PVN
• In some species
• Vasopressin predominates in SON
• Oxytocin in PVN
• Each is a product of a prohormone
• Oxyphysin gt oxytocin and neurophysin
• Pressophysin gt vasopressin and neurophysin

2
Oxytocin

• No clearly established function in males
• Transitory roles in females

3
Milk let-down reflex

• Causes milk release after parturition
• Released in response to suckling
• Sensory neurons in nipple gt spinal cord gt
  mesencephalon gt magnocellular neurons
• PVN lesion studies elec. stimulation and
  recording studies

4
Mammary glandTarget of oxytocin

• Mammary alveolus
• Epithelial cells
• Myoepithelial cells
• Lactiferous duct
• Vasculature
• Oxytocin causes myoepithelial cell contraction
• In vitro mammary explant studies
• Radiolabeled oxytocin binding studies
• Oxytocin knockout mice

5
UterusTarget of oxytocin

• Oxytocin induces labor in pregnant females
• Causes contraction of myometrium
• Endogenous signal for initiating labor?
• OT present in circulation throughout pregnancy
• OT levels increase only during final stages of
  labor

6
Uterine myometrium

• Hypothesis onset of labor is due to increased
  sensitivity of myometrium to oxytocin
• Effects of estrogen and progesterone on OT
  receptor expression
• Immunoneutralization of OT doesnt block
  parturition
• Dilation of cervix stimulates OT release
  (parabiosis experiments)

7
Vascular smooth muscle Target of oxytocin

• Can cause vasoconstriction or vasodilation,
  depending on species and vascular bed
• OT causes vasoconstriction of human umbilical
  arteries and veins

8
Other targets of oxytocin

• Can inhibit CRF-stimulated ACTH secretion in
  human males
• Can stimulate prolactin release from cultured rat
  anterior pituitary cells
• OT (along with estrogen) induces maternal
  behavior in virgin female rats
• OT released at climax of human sexual response
• Role in feeding behavior?
• Ablate PVN gt hyperphagia

9
Effects of VasopressinOsmoregulation

• Helps maintain blood osmolality
• Promotes reabsorption of water from filtrate in
  nephrons of the mammalian kidney
• AVP release triggered by increase in blood
  osmolality
• Osmoreceptors in anterior hypothalamus (POA)
  detect changes in blood osmolality

10
Effects of VasopressinOsmoregulation

• Lesion POA gt prevent AVP secretion in response to
  fluid deprivation
• Osmoreceptors exhibit specificity for solutes
  (saline, sucrose not glucose)
• Salt loading increases AVP mRNA in magnocellular
  neurons

11
Effects of Vasopressin Blood VolumePressure
Regulation

• Changes in blood volume (gt8) and pressure (gt5)
  affect AVP secretion
• Changes sensed by pressure-sensitive receptors in
  left atrium, aortic arch, carotid sinus
• Neural pathways relay info to AVP neurons
• Angiotensin II also stimulates AVP secretion

12
Effects of vasopressinAdenohypohysial Function

• AVP present in median eminence
• AVP enhances CRH-stimulated ACTH secretion
• Ultimately affects cortisol secretion gt
  sympathetic activity gt hypertension
• Equipotent with TRH in stimulating TSH secretion

13
OxytocinMechanism of Action

• One oxytocin receptor identified thus far
• In myometrial cells, oxytocin enhances
  intracellular Ca 2 levels
• Membrane calcium channels (Fig. 7-13)
• Activ of IP3 pathway
• oxytocin stimulates prostaglandin (PG) production
  by endometrium
• PGs cause luteolysis gt decreased progesterone

14
Vasopressin Receptors

• Four subtypes of receptors identified
• V1 present in vascular tissue (IP3
  prostaglandins Ca 2-calmodulin)
• V1a present in liver (IP3 gt Ca2)
• V1b present in ant.pit. (IP3 gt Ca2)
• V2 present in kidney (adenyl cyclase)

15
Kidney effects of vasopressinMechanism of
action

• AVP activates receptors on cells of collecting
  ducts
• Receptor activates cAMP pathway gt PKA
• PKA causes insertion of water channels (aquaporin
  proteins) in apical membranes of collecting duct
  cells
• AQP2 only present in intracellular vesicles of
  collecting duct cells in Brattleboro rats