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Flashcards in GH and PRL Deck (29):
1

List the hormones of the somatomammotropin family

PRL, GH and placental lactogen (hPL)

2

structure of somatommamotropins

polypeptides

3

regulation of PRL secretion

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

4

What drug can be used to prevent hypersecretion of PRL

bromocriptine, a dopamine agonist

5

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

lactotrophs- 30% of the adenohypophysis

6

How does DA inhibit PRL secretion

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.

7

Principal target of PRL

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

8

PRL transport and half life

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

9

What causes release of PRL

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

10

Describe PRL receptor binding

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.

11

PRL receptor cross reactivity

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

12

Which disease was associated with cadaver transplant of GH

Creutzfeld-Jacob disease

13

How are different forms of GH made

alternative splicing

14

GH synthesis

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

15

What proportion of the adenohypophysis contains cells that secrete GH

10%

16

Regulation of GH secretion

GHRH stimulates release of GH and somatostatin decreases its release

17

GH transport and half life

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.

18

describe the action of GH on adipose tissue

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.

19

describe the action of GH on muscle

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

20

describe the action of GH on the liver

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

21

Indirect actions of GH are mediated by ______

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

22

IGF-1 structure and receptor

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.

23

IGF-1 actions on bone/cartilage

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.

24

IGF-1 actions on muscle

stimulates proliferation, differentiation and protein synthesis

25

IGF-1 actions on adipose tissue

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

26

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

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

27

List products of metabolism which stimulate GH release

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

28

List products of metabolism which inhibit GH release

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

29

measuring GH

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.