The hypothalamo-neurohypophysial axis Flashcards
Name 2 hormones released from the neurohypophysis
Oxytocin
Vasopressin
Where do the neurones innervating the pituitary gland originate?
Supraoptic and paraventricular nuclei in hypothalamus
Magnocellular neurones
Long
Majority of neurones from hypothalamus to pituitary
Parvocellular neurones
Short
Originate from paraventricular nuclei
Terminate in median eminence/ other areas
Supraoptic neurones have Herring bodies along their axon
To store vasopressin/ oxytocin vesicles
Describe supraoptic neurone transmission
Leave hypothalamic supraoptic nuclei
Pass through median eminence
Terminate in neurohypophysis
What are the 2 types of supraoptic neurones?
Vasopressinergic
Oxytocinergic
Where do paraventricular neurones originate?
paraventricular nuclei
Some paraventricular neurones are parvocellular
Pass to other parts of brain
If VP, terminate in median eminence
Majority of paraventricular neurones are
Mangocellular
Terminate in neurohypophysis
2 types of paraventricular neurones
Vasopressinergic
Oxytocinergic
Vasopressin and CRH are both secreted from paraventricular neurones.
Are they secreted at the same anatomical location?
Yes
Vasopressin neurones terminate in median eminence where CRH is also released
How many amino acids in oxytocin and vasopressin?
9
= Nonapeptides
How different are vasopressin and oxytocin?
Only 2 different AAs
Very similar
Similar effects
Neurohypophysial Hormone Synthesis
Initially synthesized as prohormones
Cleaved to form hormones & their neurophysin proteins (released together)
How many Vasopressin signalling pathways are there?
2
What does activation of V1 receptors lead to?
Increased intracellular calcium
What does activation of V2 receptors lead to?
Increased cAMP
V1 receptor mechanism
Linked via G proteins to phospholipase C which acts on membrane phospholipids to produce IP3
Increase cytoplasmic calcium and other intracellular mediators
V2 receptor mechanism
Linked via G proteins to adenyl cyclase Which acts on ATP to form cyclic AMP Which activates protein kinase A Which activates intracellular mediators Which produce cellular response (aquaporins)
Where are V1a receptors located?
Arterial/ arteriolar smooth muscle
Hepatocytes
CNS Neurones
What do V1a receptors allow in arterial smooth muscle?
Vasoconstriction
What do V1a receptors allow in hepatocytes?
Glycogenolysis
What do V1a receptors allow in CNS neurones?
Behavioural/ other effects
Where are V1b receptors located and what do they allow?
Corticotrophs
Increase ACTH production
Where are V2 receptors located and what do they allow?
Collecting duct cells
Water reabsorption
What factors do V2 receptors on endothelial cells relate to?
Factor VIII and von Willbrandt factor
What is vasopressin also known as?
Antidiuretic hormone (ADH)
Where is vasopressins principle physiological action
Renal collecting ducts
Stimulates water reabsorption
What are the cellular responses caused by vasopressin?
Synthesis of AQP 2 molecules Move aggraphores towards apical membrane AQP 2 inserted into apical membrane Apical membrane impermeable to water until AQP 2 inserted Allows water reabsorption
Aquaporin 2 abbreviation
APQ 2
Aggraphores
Vesicles housing APQ 2
Major physiological action of oxytocin
Uterus Mammary gland (myoepithelial cells)
Minor physiological action of oxytocin
Unwanted, on:
Cardiovascular system
Kidney
Additional physiological action of oxytocin
CNS
What does oxytocin cause in the uterus?
Rhythmic contraction towards cervix
Increased local prostanoid production
Dilation of cervix
How are uterine actions of oxytocin regulated?
Suppressed by progesterone
Enhanced by oestrogen
Uterus sensitivity to oxytocin increases throughout pregnancy
Causes powerful contraction
Promotes delivery
What does oxytocin cause in the mammary gland
Contraction of myoepithelial cells
Milk ejection
How does oxytocin effect the cardiovascular system?
Pharmacologically
Transient vasodilation
Tachycardia
Constriction of umbilical arteries and veins
How does oxytocin effect the renal system?
Pharmacologically
Anti-diuresis
Secondary hyponatraemia (low sodium- vasopressin like)
How does oxytocin effect the CNS?
Physiologically
Maternal behaviour
Social recognition
“Tend and befriend”
What are the major clinical uses of oxytocin?
Induction of labour at term (IV infusion)
Prevention treatment of post-partum haemorrhage (IV) = local pressor action in uterus suppresses bleeding
Facilitation of milk let-down
Autism: social responsiveness
How does vasopressin regulate increased plasma osmolarity?
Recognised by osmoreceptors in hypothalamus
Water wants to leave cell to enter blood as sodium levels in blood rising
Cells shrink
Stimulates neurones that cause vasopressin secretion
Vasopressin causes water reabsorption in kidney
Stimulates other neurones to stimulate thirst
How does vasopressin regulate decreased blood pressure?
Change detected by baroreceptors
Baroreceptor neurone inhibits Vasopressin neurone
Low BP= Low baroreceptor firing rate= Less inhibition of vasopressin
Increased secretion of vasopressin
Vasopressin acts as vasoconstrictor
Increases BP
How is baroreceptor firing rate linked to blood pressure?
High BP = High firing rate
When is regulation of BP by vasopressin seen?
Extreme situations, as doesn’t have major effect on BP:
Haemorrhage
Dehydration
Neuroendocrine reflex arc controlling release of oxytocin
Suckling activates afferent nerves
Stimulates Oxytocin producing neurone in hypothalamus
Activates endocrine limb causing release of oxytocin
Efferent secretion of oxytocin into blood
Lack of oxytocin
Parturition and milk ejection effects induced/ replaced by other means
Lack of vasopressin
Diabetes insipidus
Excess vasopressin
Syndrome of inappropriate ADH
Diabetes insipidus taste of urine
Not sweet, insipid
2 forms of diabetes insipidus
Central (Cranial)
Nephrogenic
What is central diabetes insipidus caused by?
Absence/ lack of circulating vasopressin
What is nephrogenic diabetes insipidus caused by?
End-organ (kidneys) resistance to vasopressin
Which form of diabetes insipidus is more prevalent and more serious?
Central (cranial)
Symptoms of diabetes insipidus
Polydipsia
Polyuria
Urine very dilute (hypo-osmolar)
