L2 - Hypothalamus and Posterior Pituitary

Question 1

What general processes are regulated by the hypothalamus?

Answer 1

Pituitary functions, autonomic processes, behavioral processes, and rhythmic events

Question 2

What are the two types of neurons that are important in mediating the endocrine functions of the hypothalamus?

Answer 2

Magnocelluar and parvocellular neurons

Question 3

What are the functions of the magnocellular neurons within the hypothalamus? In which nuclei are they primarily located?

Answer 3

Magnocellular neurons are primarily located within the supraoptic and paraventricular nuclei- they synthesize oxytocin and arginine-vasopressin

Question 4

What is the hypothalamo-hypophysial tract?

Answer 4

The bridge-like structure formed by the unmyelinated axons of magnocellular neurons that project from the hypothalamus through the median eminence and ends in the posterior pituitary

Question 5

What is the function of parvocellular neurons of the hypothalamus? To where do they project?

Answer 5

Parvocellular neurons project to the median eminence and release hypophysiotropic hormones that control anterior pituitary function

Question 6

What broad classes of stimuli does the hypothalamus use to drive patterns of hormone release?

Answer 6

Environmental, neural, and hormonal

Question 7

How is circadian rhythm generated?

Answer 7

The rhythm is generated by the photo-neuro-endocrine system which consists of the retina, hypothalamic suprachiasmatic nucleus, and the pineal gland through release of melatonin

Question 8

Which hormones are released by hypothalamic magnocellular neurons? What do they regulate (generally)?

Answer 8

Oxytocin (parturition and lactation) and arginine vasopressin (water balance)

Question 9

How are oxytocin and ADH packaged and released?

Answer 9

Synthesized as the preprohormone and is post-translationally cleaved and modified, before it is packaged into secretory granules with the cleaved neurophysins

Question 10

What are neurophysins? What is their apparent function?

Answer 10

By-products of post-translational prohormone processing; appears to play an important role in transport of AVP from cell bodies to their final release from the posterior pituitary

Question 11

What is the structural difference between Oxytocin and ADH?

Answer 11

Two amino acids are different

Question 12

What are the main 3 target organs of oxytocin?

Answer 12

Lactating breast, term-pregnant uterus, brain

Question 13

What uterine stimulus triggers release of oxytocin? What is the effect?

Answer 13

Stretch of the cervix by the fetus near the end of gestation or forceful contractions of the uterus; produces rhythmic smooth muscle contractions

Question 14

What mammary stimulus triggers release of oxytocin? What is the effect?

Answer 14

Suckling of the lactating breast; contraction of myoepithelial cells–> ejection of milk

Question 15

By what mechanisms is the pregnant uterus sensitized to oxytocin?

Answer 15

Increase in oxytocin receptors, increase in gap junctions, and increase in prostaglandin synthesis (simulator of uterine contraction)

Question 16

What is Pitocin? What is it used for?

Answer 16

Synthetic analog of oxytocin that is used to induce labor or stimulate force of uterine contractions

Question 17

What is the signaling pathway evoked by binding of oxytocin to its GPCR?

Answer 17

Activation of phospholipase C, producing increase in DAG and IP3, which increases cytosolic calcium, which binds to calmodulin, activating PKC, activating myosin light chain kinase, increasing myosin ATPase activity and smooth muscle contraction

Question 18

What are the receptors for AVP and in what tissues are they found? What are the physiologic effects?

Answer 18

V1 (GPCR alpha q): Smooth muscle; V2 (alpha s): Kidney; V3- brain; conserves water and vasoconstriction

Question 19

How does AVP conserve water? What is the signaling cascade responsible for eliciting the effect?

Answer 19

AVP increases water re-absorption by stimulating the insertion of aquaporins into the cell membrane of principle cells of the collecting ducts of the kidney; AVP binds to the V2 receptor and activates adenylyl cyclase, leading to PKA activation which activates aquaporin 2 to be inserted into the apical membrane

Question 20

Which aquaporin(s) is/are under AVP regulation? Where are those aquaporins expressed?

Answer 20

Only AQP2 exclusively located in collecting ducts of the kidney

Question 21

How does AVP mediate vasoconstriction?

Answer 21

ADH binds to V1 receptors in vasculature, which is an GPCR with an alpha q subunit– activates phospholipase C –> increased calcium–> myosin light chain kinase is activated

Question 22

What stimuli evoke the release of ADH? Which stimuli is more potent?

Answer 22

Either an increase in plasma osmolarity (dehydration) or a decrease in blood volume/ pressure; more sensitive to changes in osmolarity

Question 23

How does dehydration stimulate ADH release?

Answer 23

Dehydration produces loss of intracellular water from hypothalamic osmoreceptors, which causes cell shrinkage and decreases magnocellular neuron inhibition

Question 24

How does decreased blood pressure stimulate ADH release?

Answer 24

Decreases in blood pressure decrease the firing rate of the baroreceptors, whose signal is transmitted by CN IX and X. the reduced stimulation decreases the inhibition of AVP release

Question 25

What is hyponatremia?What is the most frequent cause of hyponatremia? How is it manifested?

Answer 25

Hyponatremia occurs when level of sodium in the blood is too low; Syndrome of Inappropriate ADH secretion; low volume of concentrated urine

Question 26

What is SIADH? What can cause it?

Answer 26

Syndrome of Inappropriate ADH secretion is an increase or excess in the release of ADH, in the absence of a physiologic stimuli for its release; drug side effects, tumors, CNS disorders

Question 27

What condition results from an ADH deficiency? How is it manifested?

Answer 27

Diabetes Insipidus; Large volume of diluted urine and compensatory thirst

Question 28

What are the two etiologies of diabetes insipidus?

Answer 28

Central: Lack of ADH release and Renal: G protein mutation in AVP receptor

Question 29

How does SIADH affect plasma osmolarity?

Answer 29

Decreases it

Question 30

(iClicker ?) A pediatric surgeon is called to evaluate a newborn with distended abdomen and no intestinal sounds. What could explain this?

a) decreased intestinal stretch
b) maternal admin of magnesium sulfate
c) maternal oxytocin infusion
d) increased phospholambam phosphorylation

Answer 30

b) maternal admin of magnesium sulfate

* magnesium sulfate is a ca2+ blocker used when the mother has pre-eclampsia (high blood pressure)

Question 31

(iClicker ?) Oxytocin binds to GPCR (alpha q) leading to:

a) activation of adenylate cyclase
b) phosphorylation of the receptor
c) activation of calmodulin
d) decreased Ca2+ release from ER

Answer 31

c) activation of calmodulin

alpha q - increase PLC beta, inc. IP3, inc. DAG, inc. Ca2+, inc. PKC

Question 32

(Hypothalamus & Posterior Pituitary) Lack of AVP release would be expected to result in

a) increased urine output
b) normal urine output
c) decreased urine output
d) hyponatremia

Answer 32

a) increased urine output

no AVP => no water retention in blood

• urine: high volume, dilute
• blood: high concentrated (high osmolarity)

Question 33

(Hypothalamus & Posterior Pituitary) A patient with an excess release of ADH would present with:

a) hypernatremia
b) hyperkalemia
c) large 24 urine volume
d) hyponatremia

Answer 33

d) hyponatremia

inc. AVP => lots of water retention
- urine: concentrated, low volume
- blood: dilute (low osmolarity)

Question 34

(Hypothalamus, Posterior Pituitary) Deficiency in ADH release would result in:

a) decreased 24 urine output
b) concentrated urine
c) hyperosmolarity (blood)
d) hyponatremia

Answer 34

c) hyperosmolarity (blood)

no ADH release => no water retention

• urine: large volume, diluted
• blood: highly concentrated