Posterior Pituitary and HPL Axis

Question 1

What is the AVP pro hormone comprised of?

Answer 1

AVP + neurophysin II

Question 2

What is the oxytocin pro hormone comprised of?

Answer 2

Oxytocin + neurophysin I

Question 3

What are the two types of cells found in the paraventricular nucleus (PVN)?

Answer 3

Parvocellular

Magnocellular

Question 4

What are the only PVN cells to project to the posterior pituitary?

Answer 4

Magnocellular Neurons

Question 5

Where do parvocellular PVN neurons project to?

Answer 5

Median Eminence

Question 6

When does the cleavage of neurophysin from released hormones occur?

Answer 6

Neurophysin is cleaved from the prohormone in the secretory granules during axonal transport.

Question 7

What are the main targets of AVP?

Answer 7

Kidney and vasculature

Question 8

What is the most potent stimulus for the release of AVP?

Answer 8

Osmolarity

Question 9

What is the effect of AVP on the vasculature?

Answer 9

Causes vasoconstriction

Question 10

What is the effect of AVP on the kidney?

Answer 10

Leads to aquaporin insertion in the distal tubule that leads to increased H2O reabsorption

Question 11

What is the effect of AVP on the sympathetic nervous system?

Answer 11

Increases sympathetic tone

Question 12

What receptor pathways does AVP go through to cause vasoconstriction?

Answer 12

Phospholipase C -> Ca2+ -> Calmodulin -> MLC Kinase

Question 13

What is the major symptom of diabetes insipidus?

Answer 13

Excessive urination

Question 14

What is the most common cause of diabetes insipidus?

Answer 14

Decreased AVP release which is due to a hypothalamic or pituitary defect “central” due to trauma, cancer, or infectious disease.

Question 15

Besides a hypothalamic or pituitary defect, what may be the other cause of diabetes insipidus?

Answer 15

Decreased renal responsiveness to AVP that can be either genetic OR acquired.

Question 16

Besides a hypothalamic or pituitary defect, what may be the other cause of diabetes insipidus?

Answer 16

Decreased renal responsiveness to AVP that can be either genetic OR acquired.

Genetic - X linked mutation in the AVP receptor
Acquired - Li treatment or hypokalemia

AVP levels are NORMAL in BOTH genetic and acquired diabetes insipidus.

Question 17

What is pitocin?

Answer 17

It is artificial oxytocin used to stimulate labor

Question 18

What does the oxytocin receptor activate?

Answer 18

It is a GPCR that activates PLC and IP3 -> Ca2+ signalling

Question 19

What is the function of oxytocin?

Answer 19

Induces smooth muscle contration in breast and uterus for milk ejection and birth

Question 20

How are the structure of AVP and OXY similar?

Answer 20

They are both 9 AAs and only differ by a single AA

Question 21

What is the HPL axis comprised of?

Answer 21

Hypothalamic Arcuate Nucleus - GHRH
Pituitary Somatotroph - GH
Liver - IGF-I

Question 22

What is the function of GHRH?

Answer 22

It is made in the arcuate nucleus and functions to stimulate the release of GH from the anterior pituitary.

Question 23

What are the two forms of somatostatin?

Answer 23

There is SS14 and SS28

SS14 is found in the hypothalamus and SS28 is found in the D cells of the stomach

Question 24

What is the function of somatostatin in the brain?

Answer 24

Inhibits GHRH at the hypothalamus

Inhibits GH and TSH in pituitary

Question 25

Describe the release of somatostatin and its timing.

Answer 25

It has a pulsatile release that occurs normally at night

Question 26

What stimulates IGF-I production in the liver?

Answer 26

GH

Question 27

What is the function of IGF-I?

Answer 27

Insulin-like growth factor mediates the downstream effects of GH and also as negative feedback to INHIBIT GH release.

Question 28

What is the effect of IGF-I on various tissues like muscle/adipose/liver?

Answer 28

IGF-I acts like insulin in muscle but does not in adipose or liver because they do not have the receptors.

Question 29

At what age range does IGF-I reach its peak?

Answer 29

During puberty

Question 30

What are some of the direct effects of GH?

Answer 30

Decreases adiposity Increases gluconeogenesis/protein synthesis Increases lean body mass

Question 31

What are the effect of IGF-I (indirect effects of GH)?

Answer 31

Increases organ size and function | Increases linear growth

Question 32

What is the cause and effect of gigantism?

Answer 32

GH excess often due to a somatotroph tumor. This occurs before the closing of the epiphyseal plates and results in long bones.

Question 33

What is the cause and effect of acromegaly?

Answer 33

Similar to gigantism, but occurs around middle age. Gradual enlargement of hands and feet – leads to arthritis Changes in facial features – protuding lower jaw, enlarged lips, tongue, and nose. Possible increased organ size Most often caused by pituitary adenoma

Question 34

What is Laron Syndrome?

Answer 34

It is a form of dwarfism caused by a genetic defect in GH receptor so there is no production of IGF-I. Treatment with IGF-I can prevent dwarfism. Plasma GH levels are normal to high (lack of feedback).

Question 35

What is African Pygmy syndrome?

Answer 35

It is a form of dwarfism caused by a partial defect in GH receptor that results in some IGF-I response. Plasma levels of GH normal as the IGF-I is produced and enacts negative feedback, but there is no pubertal increase in IGF-I so growth stops here and it is hard to diagnose as children are normal until this point.

Question 36

What is the function of prolactin and its role in endocrine axes?

Answer 36

Lactotropes are not part of an endocrine axis – short loop feedback on hypothalamic dopamine; no unique stimulating factor from hypothalamus.

Question 37

What is an inhibitor of prolactin?

Answer 37

Prolactin is tonically inhibited by dopamine – early antihypertensive drugs inhibit dopamine ---- increased prolactin (galactorrhea)

Question 38

How is prolactin transported in the blood?

Answer 38

Prolactin is not bound to serum proteins and is released in response to the suckling stimulus.

Question 39

What is prolactin and inhibitor of?

Answer 39

GnRH. It is to prevent ovulation and subsequent pregnancies.

Question 40

Why can excess GH cause galactorrhea and inhibit reproduction?

Answer 40

GH and prolactin have similar structures that can be recognized by their receptors

Question 41

What is prolactin excess caused by and its effect?

Answer 41

Prolactinomas – 30-40% of all pituitary adenomas. Hyperprolactinemia Galactorrhea – milk production or discharge from breast Reproductive dysfunction - prolactin inhibits GnRH release

Question 42

What is Sheehan's Syndrome?

Answer 42

Occurs as a result of excessive blood loss/shock during childbirth. Partial pituitary destruction occurs that usually affects other pituitary cell types and leads to loss of axillary and pubic hair and prevents breast feeding due to no prolactin production.