GH and PRL

Question 1

List the hormones of the somatomammotropin family

Answer 1

PRL, GH and placental lactogen (hPL)

Question 2

structure of somatommamotropins

Answer 2

polypeptides

Question 3

regulation of PRL secretion

Answer 3

The hypothalamus tonically inhibits the secretion of PRL via PIH, or DA. If the hypothalamic influences to the anterior pituitary are prevented, the adenohypophysis will secrete much larger amounts of PRL, whereas the secretion of the other anterior pituitary hormones will not increase

Question 4

What drug can be used to prevent hypersecretion of PRL

Answer 4

bromocriptine, a dopamine agonist

Question 5

name the cells that secrete PRL and what proporption of the adenohypophysis they occupy

Answer 5

lactotrophs- 30% of the adenohypophysis

Question 6

How does DA inhibit PRL secretion

Answer 6

DA reduces release and synthesis of PRL, inhibits lactotroph cell division and DNA synthesis and increase destruction of PRL containing secretory granules (crinophagy). Inhibition of cAMP formation appears to be involved in mediating these effects.

Question 7

Principal target of PRL

Answer 7

breast- PRL plays role in production of milk. High levels of PRL lso inhibit pulsatile release of GnRH by hypothalamus. PRL receptors are located on breast, livery, ovary, testis and prostate

Question 8

PRL transport and half life

Answer 8

PRL is transported in the blood unmodified and has a short half-life of 20-30 min

Question 9

What causes release of PRL

Answer 9

Suckling of the breast, also in response to stress in males and females

Question 10

Describe PRL receptor binding

Answer 10

PRL receptors are members of the growth hormone/cytokine receptor families. Upon ligand binding, receptors dimerize, leading to the activation of the JAK/STAT pathway.

Question 11

PRL receptor cross reactivity

Answer 11

due to similar structures of PRL and GH, the PRL receptor can be stimulated by GH as well

Question 12

Which disease was associated with cadaver transplant of GH

Answer 12

Creutzfeld-Jacob disease

Question 13

How are different forms of GH made

Answer 13

alternative splicing

Question 14

GH synthesis

Answer 14

GH is synthesized as part of a prohormone. Once the signal peptide is cleaved, GH is stored in secretory granules of somatotrophs of the adenohypophysis

Question 15

What proportion of the adenohypophysis contains cells that secrete GH

Answer 15

10%

Question 16

Regulation of GH secretion

Answer 16

GHRH stimulates release of GH and somatostatin decreases its release

Question 17

GH transport and half life

Answer 17

The majority of GH circulates in an unbound form and has a half-life of 20-45 min. There is some evidence suggesting that a portion of plasma GH is bound specific binding proteins (GHBP), which are cleaved N-terminal peptides of its receptor.

Question 18

describe the action of GH on adipose tissue

Answer 18

increase lipolysis and lead to mobilization of lipid and thus an increase in plasma free fatty acids (FFAs). Eventually, the effect of GH on fat metabolism will be evidenced by a loss in subcutaneous fat. In this action GH antagonizes the action of insulin.

Question 19

describe the action of GH on muscle

Answer 19

GH has a strong anabolic action on muscle. Aminoacid transport is increased, and protein synthesis is increased

Question 20

describe the action of GH on the liver

Answer 20

Increased RNA, protein and glucose synthesi (gluconeogenesis). Further, IGF-I will be secreted, which mediates the indirect effects.

Question 21

Indirect actions of GH are mediated by ______

Answer 21

Insulin-like Growth Factor I (IGF-I), requires both GH and insulin

Question 22

IGF-1 structure and receptor

Answer 22

Structurally related to proinsulin. The IGF receptor has tyrosine kinase activity so it autophosphorylates itself and other proteins. Insulin receptor associated proteins 1 and 2 bind to the IGF receptor, then they bind to other molecules to activate MAP kinase pathway or transduction mediated by PI-3 kinase.

Question 23

IGF-1 actions on bone/cartilage

Answer 23

Long bone growth is promoted by the stimulated proliferation of epiphyseal cartilage. After puberty, the epiphyses seal and IGF-I no longer has this effect on linear growth.

Question 24

IGF-1 actions on muscle

Answer 24

stimulates proliferation, differentiation and protein synthesis

Question 25

IGF-1 actions on adipose tissue

Answer 25

stimulates uptake of glucose and inhibits lipolysis. This action of IGF is insulin like and antagonizes that of GH

Question 26

describe control of GH secretion at the level of the brain, hypothalamus, anterior pituitary and target organs

Answer 26

Brain: Increases during sleep stages 3 and 4, stress. Hypothalamus: GHRH stimulates release, somatostatin inhibits release. Anterior pituitary: GH has negative feedback at hypothalamus by stimulating somatostatin release. Targets: IGF-1 from liver has negative feedback on hypothalamus by stimulating somatostatin secretion and inhibiting action of GHRH at anterior pituitary

Question 27

List products of metabolism which stimulate GH release

Answer 27

hypoglycemia, amino acids (arginine), low free fatty acid levels, a-adrenergic agonists (clonidine), b-adrenergic antagonists (propranolol) and estrogens.

Question 28

List products of metabolism which inhibit GH release

Answer 28

hyperglycemia, high free fatty acid levels, obesity, a-adrenergic antagonists, b-adrenergic agonists as well as pharmacological doses of corticosteroids

Question 29

measuring GH

Answer 29

obtain measurements several times over the course of a day. Stimulation of GH secretion by exercise or high doses of arginine is often used to assess GH status. In addition, measurement of IGF-I levels is very helpful, especially since its levels are subject to less diurnal variation.