Endo 2 - Hypothalamo-neurohypophysial axis Flashcards
What is a hypothalamic nuclei?
a collection of cell bodies that send their axons somewhere else
State the two main hypothalamic nuclei? Where do they terminate?
Paraventricular - Neurohypophysis
Supra-optic - just above optic chiasm in neurohypophysis
Which nuclei has magnocellular neurons only?
Supra-optic.
Paraventricular have parvocellular (terminate in median eminence and other parts of brain) and magnocellular neurons (majority).
What are Herring bodies?
Along the axon, they are storage for hormones
on magnocellular neurons
What are the two neurohypophysial hormones? Structures?
Vasopressin = anti-diuretic hormone Oxytocin 9 aa (nonapeptides). Differ by 2 aa. Form a loop. Some of their functions can overlap as they are similar
Describe the synthesis of vasopressin? What other molecules are produced when the prohormone is cleaved?
Synthesised from pre-provasopressin (=pre-prohormone) then signal sequence is cleaved which gives provasopressin. Provasopressin cleaved to give arginine vasopressin, neurophysin (NP) and glycopeptide
NP is used to stabilise prohormone in herring bodies otherwise would diffuse out
For oxytocin this is the same except NP differs slightly and glycopeptide is absent
What is the main effect of VP?
Increase water reabsorption in the kidney collecting duct cells
What are other effects of VP?
Vasoconstriction CRH and ACTH release by action of parvocellular neurons CNS - behaviour Hepatic glycogenolysis Synthesis of blood clotting factors
What are the types of VP receptors? Types of cells that express them?
V1a - most important Vasculature (vasoconsriction) Brain hepatocytes (glycogenolysis) V1b Corticotrophs (ACTH production) V2 Collecting duct cells Other - endothelial cells, blood clotting, vasodilation
Mechanism of action of V1 and V2 receptors?
V1 - GqPCR
Linked via PLC - acts on phospholipids to produce IP3 (and DAG) from PIP2 –> PKC which increases [Ca2+] which produce cellular response
V2 - GsPCR
Linked via AC –> acts on ATP->cAMP —> activates PKA which activates IC mediators which produce cellular response -> AQP2
Explain how VP works on the kidney
AVP binds to V2 on collecting duct cells
Activates adenylate cyclase —> increase in cAMP —-> activate PKA
—> increased synthesis of AQUAPORIN 2
AQP2 —> assembled into aggraphores —> aggraphores migrate to apical membrane —> water moves in —> water moves out of cell down concentration gradient via AQP3 + AQP4
What are the two main functions of vasopressin? How is VP release stimulated?
Increase BP - detected by baroreceptors
Decrease plasma osmolality - detected by osmoreceptors
2 pathways control VP for the 2 different functions
What are the two main actions of oxytocin?
Uterus at parturition - contraction - delivery of baby. Sensitivity to oxytocin increases at 35 weeks. Suppressed by progesterone, enhanced by oestrogen
Breast during lactation - contraction - milk ejection
What are the other effects of oxytocin?
CVS, Kidney (VP-like), CNS (‘tend and befriend’)
What are the clinical uses of oxytocin?
Induction of labour at term
Prevention treatment for post-partum haemorrhage
Facilitation of milk let-down
Autism
