Endocrine IV: Posterior Pituitary and HPL Axis

Question 1

Oxytocin and AVP are ________ and transcribed as __________.

Answer 1

nonapeptides; preprohormones

Question 2

What is the prohormone form of AVP and oxytocin?

Answer 2

• AVP prohormone: AVP+neurophysin II

- Oxytocin prohormone: oxytocin+neurophysin I

Question 3

The PVN has 2 types of cells: _________ and _________. Only _________ neurons project to the posterior pituitary.

Answer 3

magnocellular; parvocellular; magnocellular

Question 4

What triggers AVP release from the posterior pituitary?

Answer 4

blood loss greater than 10% and a decrease in mean arterial blood pressure `

Question 5

True or false: small changes in plasma osmolality trigger AVP release AFTER stimulation of the thirst response.

Answer 5

false: small changes in osmolality trigger AVP release PRIOR to stimulation of the thirst response

Question 6

What is a major inhibitor of the HPL axis?

Answer 6

somatostatin (by inhibiting GHRH pulse frequency at level of hypothalamus; also inhibits GH release in pituitary)

Question 7

What increases vs. decreases growth hormone?

Answer 7

• stress, exercise, and starvation increase GH

- aging, high blood glucose, and obesity decrease GH

Question 8

Many downstream target organ effects of GH are mediated through what?

Answer 8

IGF-1 (somatomedins)

Question 9

GH is released in a pulsatile manner. When is it primarily released?

Answer 9

during the night while asleep

Question 10

What are the two types of dwarfism we discussed, and which hormone are they related to?

Answer 10

Laron Syndrome and African Pygmy; related to GH deficiency

Question 11

What is the implication of GH and prolactin being structurally similar?

Answer 11

This can result in non-specific binding of the GH or prolactin receptor when one of the hormones is produced in excess.

Question 12

Why can prolactin excess lead to reproductive dysfunction?

Answer 12

because prolactin inhibits GnRH release!

Question 13

For posterior pituitary hormones, what is the hormone product stored in vesicles, and what happens during release?

Answer 13

hormone + neurophysin (carrier protein) stored in granules; neurophysin is cleaved during axonal transport and release of hormone

Question 14

What is the difference b/t magnocellular and parvocellular AVP?

Answer 14

• magnocellular: axons project to posterior pituitary and release AVP into systemic circulation to regulate fluid balance
• parvocellular: axons project to median eminence and are released into hypophysial portal system to regulate mood (anxiety) and stress

Question 15

Which are more sensitive– osmoreceptors or baroreceptors?

Answer 15

Osmoreceptors, which is why AVP is primarily stimulated by an increase in osmolality but also stimulated by a decrease in BP

Question 16

How does AVP exert its vasoconstrictor effects?

Answer 16

It binds the V1 (a GPCR) receptor in vascular smooth muscle cells, resulting in contraction and increasing vascular resistance (via downstream signaling).

Question 17

How does AVP exert its water conservation effects?

Answer 17

It binds V2 receptors in the principal cells of the DT of the kidney. PKA activation phosphorylates the Aquaporin 2 channel, which is then inserted into the membrane and allows increased water permeability. Water enters the cell through AQP2 from the collecting duct and leaves the cell at the basolateral side through AQP3 and AQP4 to increase blood volume.

Question 18

Diabetes insipidus is a defect of ______.

Answer 18

AVP

Question 19

What are the 2 main causes of diabetes insipidus?

Answer 19

1. Decreased AVP release (most common): hypothalamic or pituitary defect due to trauma, cancer, or infectious disease
2. Decreased renal responsiveness to AVP: X-linked mut. in V2 receptor OR Li treatment leading to hypokalemia

Question 20

How is anterior pituitary function evaluated?

Answer 20

• Hormones must be measured in pairs (ex: ACTH and cortisol)
• Hormones must be measured at appropriate times or longitudinally
• Stimulation/inhibition tests used to assess normal feedback and pituitary function
• Predict neg. feedback effects (ex:

Question 21

What is the primary clinical presentation of SIADH?

Answer 21

hyponatremia in absence of edema

Question 22

Why is there no edema with SIADH?

Answer 22

Excess fluid volume results in lower aldosterone, less sodium uptake, more sodium excretion, and diuresis. Therefore, there is no edema because Na+ is being excreted in the urine and water is following instead of being retained in the body.

Question 23

Is SIADH usually due to primary pituitary disorder?

Answer 23

Primary pituitary disorder only accounts for 33% of patients. Other causes include CNS disorders, lung disease, extrapituitary tumors, and aldosterone deficiency.

Question 24

How can aldosterone deficiency cause SIADH?

Answer 24

AVP release is triggered by low blood volume and will be secreted despite decreases in plasma osmolality.

Question 25

What is the main function of oxytocin?

Answer 25

to induce smooth muscle contraction in breast and uterus

Question 26

How is oxytocin regulated?

Answer 26

by positive feedback loops

Question 27

Describe the components of the HPL axis.

Answer 27

• Hypothalamic RH: GHRH
• AP hormone: GH
• Peripheral organ: liver
• Peripheral hormone: IGF-I

Question 28

What is the relationship b/t IGF-I and GH?

Answer 28

• GH stimulates IGF-I in the liver, and this is an insulin-dependent process.
• IGF-I has a negative feedback effect on pituitary somatotrophs and inhibits GH synthesis/release

Question 29

What are the main targets of GH?

Answer 29

adipocytes, myocytes, hepatocytes

Question 30

What are the two forms of somatostatin and where are they found?

Answer 30

SS14 in brain (one we’re concerned about) and SS28 in intestines

Question 31

What is the goal of growth hormone?

Answer 31

to conserve protein and maintain lean body mass

Question 32

GH belongs to the same family as which other hormone?

Answer 32

prolactin (same family of peptides)

Question 33

What is the implication of the structural similarity of GH and prolactin?

Answer 33

can result in non-specific binding of GH or prolactin receptor when one of the hormones is produced in excess (ex: high levels of GH can result in GH binding to PRL receptor, causing galactorrhea)

Question 34

What are the pathological conditions resulting from prolactin excess vs. deficiency?

Answer 34

• Excess=prolactinomas

- Deficiency=Sheehan’s syndrome

Question 35

How is prolactin unique?

Answer 35

it is a lactotrope and therefore not part of a defined endocrine axis; no unique stimulating factor from hypothalamus; tonically inhibited by dopamine and also feeds back on dopamine (short loop) to inhibit its release; not bound to serum proteins