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Neurohypophysial Hormones

Neurohypophysial Hormones. Chapter 7. Neurohypophysis. Magnocellular neurons Pars nervosa 2 pr hypothal nuclei (fig 7.1) Hold secretory granules Neurohemal Traverse down infundibular stalk Post pit from neural ectoderm Pituicytes; mostly glial. Neurohypophyseal Hormones.

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Neurohypophysial Hormones

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  1. Neurohypophysial Hormones Chapter 7

  2. Neurohypophysis • Magnocellular neurons • Pars nervosa • 2 pr hypothal nuclei (fig 7.1) • Hold secretory granules • Neurohemal • Traverse down infundibular stalk • Post pit from neural ectoderm • Pituicytes; mostly glial

  3. Neurohypophyseal Hormones • Oxytocin (OT), Arg Vasopressin (AVP; ADH) • Structurally related • 9 aa’s; disulfide bridge; 3 aa tail (carboxy term) • Genes for precursor prot’s • Chromosome 20 • Gene duplication (?) • Opp DNA strands

  4. Close assoc’n w/ neurohypophysin • Posttransl’n cleavage prod of proprot • Cleavage w/in sec granule • One for each hormone • Complex before excr’n • No physio action • May be transporters • PVN cell bodies mostly prod OT; SON cells bodies mostly prod AVP • Both types found in each region • Species differ

  5. Hormone Release • Stim signals • Body sensory receptors • OT: breast; AVP: blood vessels • Afferent neurons  spinal cord, other pathways  SON, PVN cell bodies • Rostral midbrain connections  SON, PVN • Exc – cholinergic; Inh – noradrenergic • Interneurons near secretory neurons may modulate

  6. Release w/ depol’n axons • Neurosec granules fuse w/ cell membr • Ca impt • Hormones  vessels • OT may encourage own release • OT in SON, PVN  incr’d OT release • PRL impt

  7. Vasopressin Regulates Body Fluids • ECF/ICF • Homeostasis  protection ICF, cell components • IVF easiest to control • Why blood? • Why maintain blood pressure?

  8. BP can be maintained through IVF vol • Or through art smooth muscle contraction • Fluid vol control through kidney • Prox tubule: most reabs’n most water, electrolytes • Luminal membr renal endothelium has water channels (aquaporins) • Distal tubule, collecting duct can become permeable to water w/ hormonal signal • Vasopressin

  9. Vasopressin • Human arg in position 8 • Coexpressed w/ CRH in parvocell paraventric neurons • Potentiates CRH response @ corticotrophs • Can function as neurotransmitter • Antipyretic (lowers body temp) • Receptors heptahelical, G-prot coupled

  10. Osmoregulation • If incr’d body fluid osmolality (mostly Na) •  stim’n hypothal osmoreceptors • Not related to SON, PVN prod’ng cell bodies • Sensitive to blood [electrolyte] changes • Stim’d @ plasma osmolality >280 mOsm/kg • Specific • NaCl, sucrose • Not glucose, urea •  AVP rel’d

  11. If decr’d blood vol, pressure •  stim’n baroreceptors • Heart LA, aortic arch, carotid sinus • Afferent signal  vagal, glossopharyngeal nerves • Stim’n when bp decr’d >8% •  AVP released

  12. Other AVP regulators • Renin-angiotensin system • Na, so fluid osmolarity • CNS symp input • Book: both receptor signals impinge on AVP-producing cell bodies • Overall: AVP  incr’d bp by • Retention of water • Incr’d contraction vasc smooth muscle

  13. Mechanism of Vasopressin Action • In kidney collecting duct epithelium • V2 renal receptor; ad cyclase coupled • Four subtypes • Others through inositol/Ca • Book: toad bladder model • Epith sheet • Basal water barrier @ mucosal side • Analogous to renal tubule lumen • Other: serosal

  14. AVP @ serosal side •  change in water permeability •  barrier decr’d •  water transport mucosal to serosal • Withdrawal AVP  reversal

  15. In nephron collecting duct • Basal level water barrier @ luminal (apical) side • Endothelial cell vesicles in subapical area • Contain prot’s that can form water channels (aquaporins) • Membr-integral prot’s • 9 identified • Type 1 (AQ1) in prox tubule • Type 2 aquaporins • Exclusive to renal collecting duct endothelium • Biosynth • By AVP • Via CREB-mediated transcrn’l control

  16. AVP interaction w/ V2 receptor (fig 7.15) •  ad cyclase activation •  incr’d cAMP •  act’n PKA  phosph’n AQP2 mol’s •  translocation vesicles • Actin filaments, dynein •  fusion endosomal vesicles w/ apical membr •  AQP2 insertion into apical membr’s • PKA act’n also stim’s synth AQP2 prot’s • Through cAMP-linked Response Element

  17. Now water moves w/ concent gradient • Dilute urine  collecting duct endothelial cells • Another AQP (type 3; also 4?) found in basal (serosal) membr • Allow water  ISF  IVF • ISF here highly concentrated • Antiparallel to ascending limb of nephron loop • Impt to urine concent • AQP3 induced w/ dehydr’n (not linked w/ AVP) • AVP also regulates urea concent in kidney medulla (impt to urine concent)

  18. AVP also • Stim’s release ACTH  release cortisol • Synergistic w/ CRH • Stim’s release TSH; may regulate • Equipotent w/ TRH • AVP incr’s bp by regulating contraction vasc smooth muscle • Through tyr phosphorylation of enzyme-active receptor • V1 vascular receptor

  19. Oxytocin Activity Related to Reproduction • Several functions • Milk release • Uterine contraction at parturition • Vascular smooth muscle response • Maternal/mating behavior • Most specific to females • Transitory

  20. Oxytocin Hormone • Nonapeptide • Secr’n stim’d by • Cervicovaginal stretch receptor act’n • Stim’n nipple, clitoris • Psychosensory input (lactating women) • Dehydration, stress (AVP) • Secr’n inhib’d by • Ethanol

  21. OT receptor • Encoded by chromosome 3 • Heptahelical • G-prot coupled (Gaq) • PLC signaling pathway  incr’d Ca (from stores + extracell)

  22. At Mammary Gland • Suckling •  act’n sensory nerve endings •  afferent signals through spinal cord  hypothal •  OT release • OT  mammary gland myoepithelial cells (fig 7.4, 7.5) • Binding OT receptors  incr’d intramammary pressure •  milk expresion to ducts, alveoli, nipples

  23. At Uterus • Descent fetus •  cervical/vaginal stretch receptor act’n •  OT release from post pit • Positive feedback mech til birth • Get incr in both freq, amplitude of contractions

  24. Near parturition (20-39 wks), uterine myometrium more sensitive to OT • E2  incr’d OT uterine receptors  incr’d OT sensitivity • Progesterone low; can suppress OT receptor synth • BUT circ’ng OT not nec for labor initiation, maintenance • Uterine OT mRNA incr’d more in pregnancy than hypothal (rat) • Uterus may be autocrine

  25. OT binding myometrium receptors •  inhib’n Ca ATPase  Ca out of intracell stores •  IP3 involvement  Ca out of intracell stores • (with incr’d intracell Ca) act’n Ca membr channels •  depol’n myometrial cells  open voltage-gated channels •  influx extracell Ca

  26. Prolonged elevation intracell Ca •  calmodulin act’n •  kinase act’n •  phosph’n myosin •  contraction

  27. Also OT interacts w/ receptors in both myometrium + endometrium •  synth PGF2a (ovine endometrium) • Incr smooth muscle contraction • Estrogens  incr’d activity PG synthetase, so enhance PGF2a • OT-induced myometrial contractions also  endometrial PGF2a induction

  28. Progesterone involvement • Antagonizes estrogen effects • Maintains endometrium (pregnancy) • Is maintained by CL • OT  uterus  PG’s •  CL  luteal regression •  decr’d progesterone •  depress maintenance of pregnancy

  29. Also, now decr’d progesterone  decr’d antagonism of estrogen effects •  incr’d PGF2a in endometrium, •  incr’d OT-induced PGF2a in myometrium • Overall, incr’d uterine contraction

  30. Vascular Smooth Muscle • OT may constrict or relax • Depends on site • May be distinct receptor types for 2 responses • Some cross-over w/ AVP • More OT receptors in umbilical vasc • More AVP receptors in aorta vasc

  31. Maternal Behavior • OT  incr’d maternal behavior in virgin females (rat) • May need E2 • Ovariectomization negates effect • OT may be rel’d @ many brain sites at parturition • Acts as neurotransmitter • Inhibits memory/retrieval (?) • Opp AVP • Block recall pain of labor

  32. Mating Behavior/Sexual Response • Hypothal VMN controls some female mating behavior • E2  induction OT receptors • Progesterone •  incr’d OT receptor binding •  expansion brain area covered by receptors • Plasma [OT] incr’d during sexual arousal (human) • Female – incr’d uterine, vaginal smooth muscle • Male – incr’d repro smooth muscle contraction

  33. Other OT Activities • Inhib CRH-mediated ACTH secr’n (human male) • Stress response? • Stim release PRL • PRL needed to produce milk • Book: control feeding behavior

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