The hypothalamo-neurohypophysial axis Flashcards
Difference between hypothalamo- neurohypophysial axis and hypothalamo- adenohypophysial axis
Neuro= neurosecretion happens in median eminence Adeno= neurosecretion happens in posterior pituitary gland Neuro= neurones terminate in neurohypophysis (posterior pituitary) Adeno= neurones terminate at median eminence
Where do neurones originate?
Cell bodies in the supraoptic and paraventricular nuclei
What are the type of neurones in this axis?
What other type terminate elsewhere? (Origin?)
Magnocellular (large) neurones
Also parvocellular neurones originate in paraventricular nuclei+ terminate either in median eminence/ never leave brain
Supraoptic neurones
Pathway?
Features?
Types of neurones coming out from it?
Leave hypothalamic supraoptic nuclei Pass through median eminence Terminate in neurohypophysis Have Herring bodies along axon= sites of storage of vasopressors/ oxytocin EITHER VASOPRESSINERGIC OR OXYTOCINERGIC
Paraventricular nuclei
Pathway?
Types of neurones coming out from it?
Originate in paraventricular nuclei
Some parvocellular neurones pass to other parts of brain/ terminate in median eminence (adenohypophysis function affected)
But majority= magnocellular and pass to neurohypophysis
EITHER VASOPRESSINERGIC OR OXYTOCINERGIC
Vasopressin vs Oxytocin
Both have 9 amino acids (nonapeptides)
Structurally similar
2 positions= amino acids different
Synthesis, storage, release of vasopressin+ oxytocin
Pre-provasopressin has Signal peptide on it to signal to golgi to make → Pro-vasopressin (Arginine vasopressin (AVP)) in vesicles with enzymes that move along Herring Bodies→ Vasopressin+ Neurophysin+ Glycopeptide (all released)
Same for oxytocin, but neuruphysin= different structure+ no glycopeptide
Vasopressin receptors
Mechanisms?
Subcategories? Locations?
V1
Linked via G proteins to phospholipase C= acts on membrane phospholipids to produce inositol triphosphate (IP3)+ Diacyl glycerol (DAG)= increase cytoplasmic Ca2+ and other intracellular mediators (PKC)= produce cellular response
End effect= increased intracellular Ca2+
V1a: Arterial/ arteriolar smooth muscle (vasoconstriction), hepatocytes (glycogenolysis), CNS neurones (behavioural+ other effects)
V1b: Corticotrophs (work with CRH to increase ACTH production)
V2
Linked via G proteins to adenyl cyclase= acts on ATP to form cyclic AMP= activates protein kinase A= activates other intracelllular mediators= cellular response (aquaporins AQP2)
End effect= increase cAMP= activates Protein Kinase A
Collecting duct cells (water reabsorption), other effects (endothelial cells, factor viii, von Willbrant factor (both clotting)
Principal physiological action of vasopressin Location? Stimulates? Effect? Mechanism?
Renal collecting ducts
Stimulates water reabsorption
Antidiuretic effect
- VP (Vasopressin) delivered by blood to collecting duct
- Binds to V2 receptor on basolateral membrane
- Increased cAMP
- Activates PKA= activates other intracellular mediators
- Synthesis of AQP2 molecules, stored in vesicles called aggraphores
- Aggraphores move towards apical membrane which is impermeable to water
- Osmotic gradient from lumen to blood (because of Na gradient)
- H20 leaves collecting duct through AQP3 and 4 which are less to vasopressin= don’t need to regulated if AQP2 is, allow H20 to leave cell into blood
Physiological action of oxytocin
Major? Oxytocin impacted by?
Minor? Effects?
Addtional physiological? Effects?
Major= therapeutic advantage
Uterus at parturition (giving birth) (increased sensitivity of uterus to oxytocin closer to parturition)→ myometrial cells→ rhythmic contraction from fundus to cervix+ increased local prostaglandin production+ dilation of cervix→ delivery of baby; suppressed by progesterone, enhanced by oestrogen
Breast during lactation (mammary gland)→ contraction of myoepithelial cells→ milk ejection
Minor= unwanted effects
Cardiovascular system (transient vasodilation+ tachycardia)
Kidney (also some vasopressin effects) (anti-diresis+ secondary hyponatraemia (low sodium))
Constriction of umbilical arteries+ veins
Addional physiological
CNS (maternal behaviour, social recognition)
‘Tend+ Befriend’ (Women protect+ care for children, seek out and receive social support) (oestrogen promotes oxytocin release, testosterone inhibits it)
Major clinical uses of oxytocin
Induction of labour at term
Prevention treatment of post-partum haemorrhage (local pressor action in uterus suppresses bleeding)
Facilitation of milk let-down
Autism- social responsivness (still researching)
Control of vasopressin
Increased plasma osmolarity → osmoreceptors in hypothalamus shrink in response→ stimulates neurones that project onto vasopressin magnocellular cells→ stimulates vasopressin+ thirst → increased water reabsorption in nephron→ decreased plasma osmolarity
-ve feedback
Not as much as effect as above: Decrease arterial BP→ decreased baroreceptor firing rate→ reduced inhibition of baroreceptor neurone→ reduced inhibition of vasopressin secretion→ increased vasopressin release→ increased vasoconstriction→ increased blood pressure
-ve feedback
Also control from higher centres in brain (e.g. stress)
Control of oxytocin
Suckling→ receptors around nipple activates neural afferent limb→ stimulates oxytocin producing nerves in hypothalamus→ efferent secretion of oxytocin in neurohypophysis into blood into peripheral tissue through endocrine efferent limb→ promotes milk ejection
Lack of oxytocin
Parturition+ milk ejection effects induced/ replaced by other means (not that much of an issue)
Lack of vasopressin
Another stimulus that causes the effect?
Signs of the effect?
Diabetes insipidus (centrally/ cranially caused) No vasopressin
Diabetes insipidus also caused by kidney resistance to vasopressin (nephrogenically caused, less serious because still vasopressin produced)
Polydipsia (increased thirst)
Polyuria (large volumes of urine)
Hypo-osmolar (Urine= very dilute)
