The hypothalamo neurohypophysial axis (3) Flashcards
What are the two types of hypothalamic nuclei
paraventricular nuclei (axons pass through median eminence and terminate in the neurohypophysis) or the supraoptic nuclei (axons pass through the median emninence and terminate just above the optic chiasma in the neurohypophysis)
what are the two types of hypothalamic neurones within the paraventricular nuclei
Magnocellular neurones (larger) and they terminate in the neurohypophysis. Parvocellular neurones (smaller)which terminate either in primary capillary plexus in the median eminence or in the other parts of the brain
what two molecules is the neurohypophysis associated with
vasopressin and oxytocin
What neurones secrete vasopressin
Suprachiasmatic Nucleus and Vasopressinergic neurones
Are suparoptic neurones magnocellular or parvocellular
magnocellular
Features of Supraoptic neurones
They leave the hypothalamic supraoptic nuclei. Pass through the median eminence. They have herring bodies
which are specific to magnocellular neurones from the supraoptic and paraventricular nuclei. They release neurosecretions (hormones) in the neurohypophysis where they terminate. Molecules can be released from the herring bodies. They are either vasopressinergic or oxytocinergic
What are herring bodies
granules that accumulate the newly synthesised hormones within the
axon/dendrites, forming swellings which then release the hormones into the general circulation
Features of paraventricular neurones
Originate in paraventricular nuclei. Paraventricular neurones have a magnocellular AND a parvocellular component. Some parvocellular vasopressinergic neurones terminante in median eminence. Some parvocellular neurones pass to other parts of the brain. The majority of them are magnocellular and these pass down to the neurohypophysis. They are either vasopressinergic or oxytocinergic.
which neurones have herring bodies
magnocellular neurones (supraoptic)
What neurones secrete oxytocin
Oxytocinergic neurones
What are the differences between oxytocin and arginine vasopressin (AVP)
AVP has Phenylalanine instead of Isoleucine. AVP has Arginine instead of Leucine
So they differ by two amino acids. AVP prohormone is cleaved to produce three molecules (AVP + Neurophysin + Glycopeptide). Oxytocin prohormone is cleaved to produce two molecules (Oxytocin + Neurophysin)
What are the similarities betwee oxytocin and arginine vasopressin (AVP)
They are both nonapeptides. Both have a ring structure with 6 amino acids and a small attached chain. They are both initially synthesised as prohormones. Their prohormones are cleaved to form hormones and their neurophysin protein
What is the synthesis of vasopressin
Pre-prohormone is pre-provasopressin. This is synthesised and then processed in granules (like the herring bodies) to form pro vasopressin
(pro-hormone). Prohormone breaks down into: Arginine Vasopressin (AVP), Neurophysin (NP)
and Glycopeptide. These products are formed in equimolar amounts. This break down takes place in the nerve axon.
What is the synthesis of oxytocin
Pre-prooxytocin splits into pro-oxytocin. The pro-oxytocin is further processed to form oxytocin and a slightly different neurophysin. It does not have glycopeptide.
What are the different vasopressin receptors
V1a and V1b. V2
how do hormones affect the brain
by entering the cerebrospinal fluid
Where is V1a receptor found
Vascular smooth muscle (vasoconstriction). Hepatocytes (glycogenolysis). CNS parvocellular neurones (behavioural effects)
Where is V1b receptor found
Adenohypophysial corticotrophs (ACTH production)
Where is V2 receptor found
Collecting duct cells (water reabsorption). Other unidentified sites (e.g. endothelial cells, blood clotting factors VIII and Von Willbrandt factor
What does the V1 receptor do
A Gq protein linked receptor. Linked via G proteins to phospholipase C (PLC). Once activated, PLC converts PIP3 to IP3 and DAG which increase cytoplasmic [Ca2+] and activate other mediators such as Protein Kinase C (PKC) which produce cellular response
What does the V2 receptor do
A Gs protein linked receptor. Linked via G protein to Adenylate Cyclase. Once activated, adenylate cyclase converts ATP to cAMP. cAMP activates Protein Kinase A (PKA). PKA activates other intracellular mediators which produce cellular responses (recruitment of aquaporins which causes the antidiuretic effect)
What is the physiological action of vasopressin
Its principle physiological action is in the renal collecting duct (principle cells) where is stimulates water reabsorption. This results in its antidiuretic effect. Controls final concentration of urine
What are the other actions of vasopressin
vasoconstriction, CNS effects, acting on neurotransmitters, corticotrophin release, synthesis of blood clotting factors, hepatic glycogenolysis
how does vasopressin control renal water reabsorption
V2 receptors are found in the basolateral membrane. Vasopressin binds to the V2 receptor and activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP. cAMP activates protein kinase A which stimulates the synthesis of AQUAPORIN 2 molecules
Why do cells need aquaporins
All cells need aquaporins to allow the movement of water across the cell membrane
What kind of aquaporin is aquaporin 2 (AQP2)
a vasopressin dependent aquaporin
What happens when Aquaporin 2 is synthesised, under the influence of vasopressin
Aquaporins assemble into accumulations called Aggraphores.
These migrate to the apical membrane (facing the inside of the collecting duct). AQP2 is inserted into the membrane. AQP2 then acts as protein channel for water absorption from the tubule lumen into the cell. Water is transported out of the cells and into the blood via AQP3 and AQP4
An osmotic gradient is needed for the movement of water from the collecting duct, through the principal cells and into the blood
Why is an osmotic gradient needed for the vasopressin physiological action
An osmotic gradient is needed for the movement of water from the collecting duct, through the principal cells and into the blood
describe the control of vasopressin in water reabsorption
Increased plasma osmolality stimulates osmoreceptors leading to stimulation of vasopressinergic neurones. More vasopressin is released. More water is reabsorbed. Plasma osmolarity returns to normal. Stimulus is removed. Vasopressin is switched off.
what is dehydration
increase in plasma osmolality
Osmolality
measure of the concentration of osmotically active particles in the blood
Why are osmoreceptors circumventricular organs
they must be in contact with vasopressinergic neurones but also with the blood so they lie outside the blood-brain barrier
describe the control of vasopressin in vasoconstriction
fall in blood pressure is a massive stimulus for VP. When the blood pressure falls there is decreased baroreceptor activity. Therefore there is decreased inhibition of VP. More VP is released. So sympathetic activity increases because the baroreceptors are linked to the sympathetic nervous system which is the neural way in which vasoconstriction is controlled.
What are baroreceptors
stretch receptors that are stimulated by an increase in pressure
What are the major physiological actions of oxytocin
act on the uterus during parturition by causing the myometrial cells to contract to allow the delivery of baby. Also act on the breast during lactation by causing the myoepithelial cells to contract. This causes milk ejection.
what stimulates milk production
prolactin
what stimulates milk ejection
oxytocin
what are the other actions of oxytocin
cardiovascular system- it causes transient vasodilation and tachycardia and constriction of umbilical arteries and veins. kidney - anti diuresis and secondary hyponatraemia. CNS - maternal behaviour and social recognition
What does oxytocin do in the uterus
it promotes rhymic contraction from the fundus to the cervix. it increases local prostanoid production. it dilates the cervix
what effects the uterine actions of oxytocin
progesterone suppresses it and oestrogen enhances is. most marked in late stages of pregnancy
What is the endocrine efferent limb of the neuroendocrine reflex arc
It goes to the neurohypophysis where it stimulates the production of oxytocin causing contraction of the myoepithelial cells in the breast resulting in milk ejection
what are the major clinical uses of oxytocin
induction of labour at term. prevention treatment of post partum haemorrhage. facilitation of milk let-down. autism- social responsiveness
what happens if there is a lack of oxytocin
doesn’t cause major issues. parturition and milk ejection effects can be induced or replaced by other means
what happens if there is a lack of vasopressin
Diabetes Insipidus - Characterised by polydipsia and polyuria. Central Diabetes Insipidus is when - no vasopressin is produced. Nephrogenic Diabetes Insipidus is when the kidneys are resistant to vasopressin.
what happens when there is too much vasopressin
SIADH (Syndrome of Inappropriate ADH)
Too much ADH produced. Decreases plasma osmolality. Urine is concentrated
