4 The Hypothalamo-Neurohypophysial Axis Flashcards
Q: How do the posterior and anterior pituitary glands differ in terms of where neurosecretion occurs?
A: ant= median eminence
post= project all way down to posterior pituitary gland
Q: Describe the principle features of the hypothalamo-neurohypophysial system with the aid of a diagram.
A: neural input
paraventricular nuclei // supra-optic nuclei
superior hypophysial artery // median eminence // mammillary body
hypophysial portal vessel
inferior hypophysial artery
pituitary cells |
\/
vasopressin // oxytocin
anterior pituitary // posterior pituitary
Q: What are the 2 types of nuclei in the hypothalamo-neurohypophysial system?
A: supraoptic and paraventricular
(where cell bodies lie)
are the 2 different types of populations where each is a group of neurones
Q: What is the main neurone type in the hypothalamo-neurohypophysial system? Where do they terminate?
A: magnocellular, neurohypophysis (posterior pituitary gland)
Q: What is the less common neurone type in the hypothalamo-neurohypophysial system? Where do they terminate? Where do they originate? What do they secrete?
A: paravocellular- exception since ends in median eminence or another part of brain
originate from paraventricular nuclei
vasopressin
Q: Describe supraoptic neurones including structure. (5)
A: equipment to make hormones is in cell body (most neurones secrete vasopressin or oxytocin)
1 leave hypothalamic supraoptic nuclei (where they originate)
2 pass through median eminence
3 terminate in neurohypophysis (end)
herring bodies are present along the axon
Q: What are herring bodies?
A: storage sites for posterior pituitary hormones (lie along axon)
Q: Describe paraventricular neurones including structure. (5)
A: 1 originate in paraventricular nuclei
2 majority of neurones are magnocellular -> pass down to neurohypophysis
3 some (parvocellular) neurones pass to other parts of brain
4 some (parvocellular) VP neurones terminate in median eminence
5 are either vasopressinergic or oxytocinergic
Q: Compare vasopressin and oxytocin in terms of their chemical structure. (4)
A: both are simple peptide with a loop and a tail
differ by 2 aa (vaso has Phe and Arg while oxy has Ile and Leu)
contain disulphide bridges (one) in loop
are nonapeptides since 2-20 aa present
Q: How is vasopressin synthesised? (3)
A: pre-prohormone first made in cell body of either supraoptic or paraventricular nucleus; pre-vasopressin which contains signal peptide;SP at start - directs it to where it needs to go
–signal peptide quickly lost as moves towards axon–> prohormone; provaspressin
–cleaved–> vasopressin;AVP (arginine vasopressin + neurophysin;NP + glycopeptide;GP
Q: Where does neurophysin come from and why is it important?
A: when provasopressin is cleaved
important in maintaining vasopressin/oxytocin stability- stops it moving out of neurone/herring body and stops degradation by enzymes
Q: How does vasopressin synthesis differ from oxytocin synthesis?
A: vasopressin has same sequence as oxytocin synthesis, except that the neurophysin differs slightly (by product when prohormone is cleaved) and the glycopeptide is absent (for oxytocin)
Q: How do the 2 types of vasopressin receptor vary? Action. Linked to _ via _. What does this do- cascade? What’s the type of response produced?
A: V1 receptor- vasoconstriction action
linked via G proteins to phospholipase C- acts on membrane phospholipids to produce inositol triphosphate (IP3) and diacyl glycerol (DAG)
increases cytoplasmic [Ca^2+] and other intracellular mediators (PKC)
which produces cellular response
V2 receptor- antidiuretic action
linked via G proteins to adenyl cyclase- acts on ATP to produce cAMP which activates protein kinase A which activates other intracellular mediators
which produces cellular response (aquaporins, AQP2)
Q: What is vasopressin also known as?
A: anti-diuretic hormone
Q: What is the effect of vasopressin receptor V1a and V1b in different target cells? (3,1)
A: V1a
main= arterial/arteriolar smooth muscle (vasoconstriction)
hepatocytes (glycogenolysis)
CNS neurones (behavioural and other effects)
V1b
corticotrophs (ACTH production)
Q: What is the effect of vasopressin receptor V2? (4)
A: main= collecting duct cells (water reabsorption)
other effects (endothelial cells, factor VII and von willeband factor)
Q: What is the principle physiological action of ADH/vasopressin? (3)
A: is in renal collecting duct (principle cells)
stimulates water reabsorption
resulting in its antidiuretic effect
Q: How does vasopressin work in principle cells/collecting duct? Include basic diagram. (8)
A: V2 receptors are
- Vasopressin binds to the V2 receptor (basolateral membrane)
- activates adenylate cyclase-> converts ATP to cAMP
- cAMP activates protein kinase A which stimulates the synthesis of AQUAPORIN 2 molecules
((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 luminal 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 (aren’t really affected by vasopressin)
- An osmotic gradient is needed for the movement of water from the collecting duct, through the principal cells and into the blood
diagram; principle cell (lines kidney tubule)
osmotic gradient across cell —->
tubule lumen; apical membrane | cell | basolateral (serosal) membrane; plasma
Q: What are the physiological actions of oxytocin (target cells)? (4) Unwanted effects on? (2)
A: major- therapeutic advantage (relating to the healing of disease)
- uterus (contraction)
- mammary gland - myoepithelial cells
minor- unwanted effects
- cardiovascular system
- kidney
additional physiological
-CNS
Q: When does oxytocin levels spike in women?
A: end of pregnancy
Q: What are the 2 main groups of target cells for oxytocin? What action occurs?
A: Uterus during parturition (childbirth)- myometrial cells- contraction -> delivery of baby
Breast during lactation- myoepithelial cells (produce milk)- contraction -> milk ejection
OXYTOCIN IS A CONTRACTOR MOLECULE - it causes constriction
Q: Explain oxytocin’s physiological action on the uterus. (3) What enhances and suppresses action?
A: promotes
rhythmic contraction; fundus -> cervix
increased local prostanoid production
dilation of cervix (opens birth channel -> delivery)
enhanced by oestrogen
suppressed by progesterone
Q: What is a fundus?
A: the part of a hollow organ (such as the uterus or the gall bladder) that is furthest from the opening
Q: What are prostanoids? When are they made? Action? (2)
A: lipid mediators generated by the action of cyclooxygenase
are generated widely in response to diverse stimuli
acting in a paracrine or autocrine manner
Q: How does the sensitivity of the pregnant uterus to oxytocin change throughout the pregnancy? Why?
A: graph
contractile response to oxytocin (y) and weeks of gestation (x)
0 to 20 is horizontal
stays until around 33 then increases till end (straight like / )
increases near end of term- reason= oestrogen also goes up towards pregnancy end (oest stimulates production of oxytocin receptors and hence uterus is more sensitive to oxytocin)
Q: Explain oxytocin’s physiological action on the mammary gland.
A: contraction of myoepithelial cells leads to milk ejection
Q: What are the 3 physiological actions of oxytocin except uterine contraction and lactation? (1,2,2)
A: cardiovascular- pharmacological
constriction of umbilical arteries and veins (important as the foetus is delivered and moves away from the need of the placenta)
renal- pharmacological
anti-diuresis
secondary hyponatraemia (occurs when sodium levels are low)
CNS- physiological
maternal behaviour
social recognition
Q: What breaks down collagen (has formed tight membrane that helps child in utero) and allows delivery?
A: prostaglandins particularly PGE2
Q: Describe the female pattern response driven by oxytocin. What inhibits/has positive effect on oxytocin?
A: tend and befriend (typical behavioural stress response = fight/flight which is quite a male pattern response)
tend; women protect and care for their chn
befriend; women seek out and receive social support
testosterone tends to inhibit
oestrogen tends to have a positive effect on oxytocin
Q: What are 3 major clinical uses of oxytocin?
A: induction of labour at term
prevention treatment of post-partum haemorrhage
facilitation of milk let-down
autism - social responsiveness?
Q: What are the 2 homeostatic methods of control of vasopressin? What are they based on (stimulus)?
A: 2 methods to control release since 2 major functions
Water Reabsorption based on plasma osmolality
Vasoconstriction based on arterial bp
Q: Define plasma osmolality.
A: concentration of osmotically active particles in blood
Q: Explain the homeostatic method of control of vasopressin where plasma osmolality is the stimulus. (6)
A: stimulus of high plasma osmolality (dehydration) received by osmoreceptors in hypothalamus - when higher osmolality in blood than neurone ->
cell body of neurone loses water and shrinks ->
stimulates neurone to fire
- > more vasopressin (ADH) in blood
- > more aquaporins -> increases water absorption
- > decreases plasma osmolality (response)
Q: Explain the homeostatic method of control of vasopressin where arterial blood pressure is the stimulus. (5)
A: stimulus of decreased arterial bp detected by baroreceptors/volume receptors which have
an inhibitory effect on vasopressin and firing rate is proportional to bp therefore if bp falls you get less inhibitory effect on ADH
- > more vasopressin produced
- > increased vasoconstriction
- > get increased bp (response)
Q: What is the neuroendocrine reflex arc? Describe it in relation to oxytocin. (6)
A: afferent nerve carries information (stimulus) -> efferent nerves (independent of brain) -> induce response
endocrine effect = doesn’t require brain
direct efferent effect -> produce oxytocin
stimulus; suckling -> neural afferent limb -> hypothalamus (neurone bundle) -> nerve to neurohypophysis -> produce oxytocin -> contraction of the myoepithelial cells in the breast resulting in milk ejection
Q: What does lack of oxytocin lead to?
A: parturition and milk ejection effects induced/replaced by other means
Q: What does lack of vasopressin lead to?
A: diabetes insipidus
symptoms of diabetes and little vasopressin are similar hence name
Q: What are vasopressin and oxytocin?
A: neurohypophysial hormones
Q: What causes diabetes insipidus? (2)
A: 2 forms
absence/lack of circulating vasopressin
|
\ / central (cranial) form (less severe but more difficult to treat)
|
\ /
diabetes insipidus
/ \
| nephrogenic form (often drug induced cause)
/ \
| end-organ (kidneys) resistance to vasopressin (vasopressin is still produced)
causes- headtrauma, certain tumours, autoimmune
Q: What are the symptoms of diabetes insipidus? (3) How do you treat it?
A: polydipsia (increased thirst)
polyuria (large volumes of urine)
urine is very dilute (hypo-osmolar)
drink more water- not particularly debilitating disease if you have access to clean water
