3- The hypothalamo-neurohypophyseal axis: posterior pituitary Flashcards
How does ADH work in the collecting duct
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
• All cells need aquaporins to allow the movement of water across the cell
membrane
• There are 9 types of aquaporin but AQUAPORIN 2 is the vasopressin
dependent aquaporin
• Aquaporins assemble into accumulations called Aggraphores
• Under the influence of vasopressin, aggraphores migrate to the apical
membrane (facing the inside of the collecting duct)
• Once the channels are inserted into the membrane, then water can move into the cells
• 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
How can ADH reduce a fall in blood pressure
Fall in blood pressure is a massive stimulus for vasopressin
• BARORECEPTORS are stretch receptors that are stimulated by an increase in
pressure
• There is an inherent activity from the baroreceptors along the neurones to the brain, when the blood pressure falls the activity slows down - it removes a tonic inhibition of VP release (like releasing a brake)
• These same baroreceptors are linked to the sympathetic nervous system which is the neural way in which vasoconstriction is controlled
• Baroreceptors decreased activity –> decreased inhibition –> increased vasopressin release –> increased sympathetic activity
How does ADH cause water reabsorbtion
Dehydrated –> vasopressin released –> more water reabsorption –> plasma osmolality returns to normal –> stimulus removed –> vasopressin switched off
How does oxytocin cause uterine contractions
Oxytocin is released in massive amounts during delivery - may be released due to an increased stress on the uterine wall
• Oxytocin acts on receptors on the smooth muscle cells in the uterus to cause contraction which facilitates delivery
Rhythmic contraction; fundus cervix
Increased local prostanoid production
Dilation of cervix
Uterine actions of oxytocin
Suppressed by progesterone
Enhanced by oestrogen
How is oxytocin involved in lactation
Prolactin stimulates milk production but it doesn’t cause milk ejection
• The ducts and alveoli involved in the synthesis of milk are surrounded by
contractile myoepithelial cells that have myoepithelial receptors
• The suckling of the baby stimulates oxytocin release which makes the
myoepithelial cells contract
• OXYTOCIN CAUSES MILK EJECTION
What other effects can oxytocin have
CARDIOVASCULAR - pharmacological
Transient vasodilation & tachycardia
Constriction of umbilical arteries and veins
RENAL - pharmacological
Anti-diuresis and secondary hyponatraemia, i.e. vasopressin-like
CNS – physiological **
Maternal behaviour, social recognition
What are some clinical uses of oxytocin
I NDUCTION OF LABOUR AT TERM
controlled i.v. infusion
•PREVENTION TREATMENT OF POST-PARTUM HAEMORRHAGE
Slow i.v. injection/infusion
Local pressor action in uterus suppresses bleeding
•FACILITATION OF MILK LET-DOWN
Intranasal spray
•AUTISM – SOCIAL RESPONSIVENESS??
Intranasal spray
What is the neurohypophysis
The neurohypophysis is made up of nerve axons and some other cells
• The nerves have their cell bodies in the hypothalamus and their nerve axons
pass down through the pituitary stalk into the neurohypophysis.
Describe hypothalamic nuclei
Hypothalamic Nuclei - a collection of cell bodies which send their axons to a particular place
• TWO main groups of cell bodies:
Paraventricular Nucleus - located close to the 3rd ventricle
Supraoptic - lying above the optic chiasma
What are the 2 main molecules associated with neurohypophysis
Vasopressin
Oxytocin
What are the 2 main types of neurone
MAGNOCELLULAR
Cell bodies in the paraventricular and supraoptic nuclei Terminate in the neurohypophysis
LARGE
• Parvocellular
Average sized
Parvocellular neurones that originate in the paraventricular nucleus terminate in the median eminence or in other parts of the brain
Describe supraoptic neurones
Supraoptic neurones are magnocellular and terminate in the neurohypophysis
• They release neurosecretions in the neurohypophysis where they terminate - the neurosecretions are hormones because they are released into the general circulation
• They have HERRING BODIES which are specific to magnocellular
neurones from the supraoptic and paraventricular nuclei
• Herring Bodies - areas where the neurosecretions can be stored on the way down to the neurohypophysis
• Molecules can be released from the herring bodies
• Supraoptic neurones are EITHER vasopressinergic or oxytocinergic
Describe paraventricular neurones
Paraventricular neurones have a magnocellular AND a parvocellular component
• Magnocellular neurones coming from the paraventricular nuclei terminate in the neurohypophysis
• The magnocellular neurones have herring bodies and they release neurosecretions into the general circulation
• Parvocellular neurones are also EITHER vasopressinergic or oxytocinergic
• Some parvocellular neurones will go to other parts of the brain and others will terminate in the median eminence
How is vasopressin synthesised
• Pre-prohormone —> Prohormone —> Hormone
• Prohormone breaks down into:
Vasopressin (Arginine Vasopressin - AVP)
Neurophysin (large protein which is specific to the provasopressin molecule)
Glycopeptide (may be a prolactin releasing factor but little is known about it)
• This break down takes place in the nerve axon
• Pre-prooxytocin splits into TWO
• Oxytocin has a slightly different neurophysin and it DOES NOT have
glycopeptide
Describe the structure of arginine vasopressin and oxytocin
Some animals have Lysine Vasopressin instead of Arginine Vasopressin
• AVP is similar in structure of Oxytocin but it has the following DIFFERENCES:
AVP has Phenylalanine instead of Isoleucine
AVP has Arginine instead of Leucine
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)
• AVP and Oxytocin have the following SIMILARITIES:
They are both nonapeptides
They are both initially synthesised as prohormones
Their prohormones are cleaved to form hormones and their neurophysin protein
