GH and PRL Flashcards
List the hormones of the somatomammotropin family
PRL, GH and placental lactogen (hPL)
structure of somatommamotropins
polypeptides
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
What drug can be used to prevent hypersecretion of PRL
bromocriptine, a dopamine agonist
name the cells that secrete PRL and what proporption of the adenohypophysis they occupy
lactotrophs- 30% of the adenohypophysis
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.
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
PRL transport and half life
PRL is transported in the blood unmodified and has a short half-life of 20-30 min
What causes release of PRL
Suckling of the breast, also in response to stress in males and females
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.
PRL receptor cross reactivity
due to similar structures of PRL and GH, the PRL receptor can be stimulated by GH as well
Which disease was associated with cadaver transplant of GH
Creutzfeld-Jacob disease
How are different forms of GH made
alternative splicing
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
What proportion of the adenohypophysis contains cells that secrete GH
10%
Regulation of GH secretion
GHRH stimulates release of GH and somatostatin decreases its release
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.
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.
describe the action of GH on muscle
GH has a strong anabolic action on muscle. Aminoacid transport is increased, and protein synthesis is increased
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.
Indirect actions of GH are mediated by ______
Insulin-like Growth Factor I (IGF-I), requires both GH and insulin
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.
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.
IGF-1 actions on muscle
stimulates proliferation, differentiation and protein synthesis
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
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
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.
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
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.
