Pituitary Hormone Function (PRL/GH)

Question 1

Prolactin

Answer 1

its secretion is tonically inhibited by secretion of PIH, or DA, from hypothalamus

Question 2

what cells secrete PRL

Answer 2

lactotrophs, comprise bout 30% of adenohypophysis

Question 3

Action of PRL

Answer 3

targets mammary glands in breast for milk secretion and high levels also inhibit pulsatile secretion of GnRH by hypothalamic neurons

Question 4

when is prolactin released

Answer 4

suckling of the breast in females and in response to stress in males/females

Question 5

prolactin receptor

Answer 5

members of growth hormone/cytokine receptor families

• upon ligand binding, receptors dimerize to activate JAK/STAT pathway
• human PRL receptors similar to GH receptors and are well stimulated by GH

Question 6

importance of growth hormone

Answer 6

fundamental for postnatal growth, stimulates somatic growth and regulates metabolism

Question 7

what type if hormone is GH

Answer 7

peptide hormone and secretory protein

• can generate alternative forms via splicing
• synthesized as part of a prohormone. Once signal peptide cleaved, it is stored in secretory granules of somatotrophs of adenohypophysis

Question 8

what hormones influence secretion fo GH

Answer 8

GHRH adn somatostatin have opposing actions

• GHRH stimulation increases cAMP levels while somatostatin decreases cAMP levels

Question 9

most of GH in blood is in what form

Answer 9

unbound; half life of 20-45 min

• some evidence a portion of plasma GH bound specific binding proteins (GHBP), which are cleaved N-terminal peptides of its receptor

Question 10

in what form is prolactin in the blood

Answer 10

transported in blood unmodified. Half life of 20-30 min

Question 11

Direct actions of GH (metabolic effects)

Answer 11

• Adipose: increase lipolysis and mobilization of lipid to increase plasma free fatty acids; antagonizes action of insulin due to eventual loss of subcutaenous fat
• Muscle- strong anabolic action; increased amino acid transport and protein synthesis
• Liver- increased RNA, protein, and glucose synthesis. IGF-I will be secreted to mediate indirect effects. Increased glucose mainly from increased gluconeogenesis not glycogenolysis

Question 12

Generally speaking, what are GH’s effects

Answer 12

anti-insulin like, i.e. glucose uptake decreased and plasma glucose levels rise

Question 13

Indirect actions of GH

Answer 13

besides metabolic, these effects are on muscle and skeletal growth mediated by insulin-like growth factor (IGF).

Question 14

IGF

Answer 14

• powerful mitogen/growth-promoting agent structurally related to proinsulin and has many insulin-like actions
• levels increase slowly from birth to puberty when much more pronounced elevation
• 2 forms (IGF-I and IGF-II), where IGF-I predominant form in postnatal tissues
• production of IGF in a number of tissues requires GH and insulin

Question 15

IGF receptors

Answer 15

belong to EGF/Insulin receptor family and contain inherent tyrosine kinase activity and upon ligand binding can readily phosphorylate themselves and other proteins of signal transduction pathway
- major path activated by IGF receptors is initiated by binding of insulin receptor associated proteins 1 and 2 (IRS I and II). IRS can bind to other molecules to activate either MAP kinase pathway or transduction mediated PI-3 kinase

Question 16

GH actions mediated by IGF-I

Answer 16

• bone/cartilage: long bone growth promoted by stimulated proliferation of epiphyseal cartilage. After puberty, epiphyses seal and IGF-I no longer has this effect on linear growth
• Muscle: stimulates proliferation, differentiation and protein synthesis
• Adipose tissue- stimulates uptake of glucose and inhibits lypolysis. This action is insulin like and antagonizes GH

Question 17

control of GH secretion besides IGF-I

Answer 17

other stimuli for GH secretion: hypoglycemia, amino acids (arginine), low FFA levels, alpha adrenergic agonists, beta adrenergic antagonists, estrogens
- opposites inhibit GH secreiton