Physio 2

Question 1

growth hormone

Answer 1

single chain polypeptide. produced in anterior pituit. 20 minute half life.

Question 2

hypothalamic control of GH secretion

Answer 2

GHRH stimulates, somatostatin inhibits. integration results in episodic pulsatile secretion.

Question 3

GHRH

Answer 3

increases GH gene transcription, promotes GH release, stimulates production of GHRH receptor, stimulates somatostatin release

Question 4

somatostatin

Answer 4

decreases pulse freq, decreases pulse amplitude, no impact on GH synth, inhibits GHRH release

Question 5

ghrelin

Answer 5

made in stomach and pancreas. stimulates hunger. levels increase before meals, decrease after, acts on growth hormone secretagogue receptor.

Question 6

pulsatile secretion of GH over lifespan

Answer 6

pulses primarily at night. number of pulses per day stays nearly constant. larger pulse amplitude during puberty. exercise can cause a surge of GH. disrupting sleep can cause lack of GH

obesity decreases number and duration of GH pulses.
fasting increases number and amplitude of GH pulses.

Question 7

stimulators of GH secretion

Answer 7

sleep, exercise, sex steroids, fasting, amino acids, stress, alpha adrenergic agonists, dopamine agonists

Question 8

inhibitors of GH secretion

Answer 8

IGH-1, obesity, glucocorticoids, hyperglycemia, free fatty acids, GH, beta adrenergic agonists

Question 9

GH activation of receptor

Answer 9

binding of GH changes arrangement of receptor dimer and activates JAK2. JAK2 phosphorylates and activates STAT transcription factors. STAT activates CISH, a GH target gene

Question 10

effects of GH on liver, adipose, skeletal muscle, and brain

Answer 10

liver: stimulates IGF-1 production, and stimulates hepatic glucose production
adipose: GH stims release and oxidation of fatty acids and reduces lipogenesis
skeletal muscle: GH stimulates AA uptake and incorporation into protein, and stims cell proliferation
brain: affects mood and behavior

Question 11

effect of GH on bone

Answer 11

GH supports the differentiation of mesenchymal stem cells into chondrocytes and maturation of chondrocytes. this leads to bone formation

Question 12

IGH-1

Answer 12

stimulates growth through autocrine, paracrine, and endocrine methods. negative feedback to the hypothalamus and pituitary down regulates GH secretion. used as the primary screening test for GH deficiency (levels are more stable and reflective of GH levels)

Question 13

signaling pathways activated by IGF-1

Answer 13

dimerization of IGF-1 receptor leads to autophosphorylation. this recruits IRS-1 and Shc, both of which get phosphorylated. this recruits other proteins leading to the activation of PI3K and Ras/MAP kinase pathways that regulate cellular transcription

Question 14

growth hormone deficiency causes

Answer 14

rare causes. any defect affecting hypothalamo-pituitary function, mutations in GH-1 gene, brain injury, absence of pituitary stalk etc..
causes extremely slow growth rate of less than two inches a year

Question 15

Laron syndrome

Answer 15

point mutation or deletion in GH receptor. leads to low IGF-1 concentration, but normal or elevated GH concentration. severe post natal growth failure. treatable with rhIGH-1

Question 16

gigantism

Answer 16

usually pituitary giants. too much GH in life. usually have hyperglycemia and 10% develop diabetes mellitus

Question 17

acromegaly

Answer 17

growth hormone secreting adenomas cause this. effects vary. protrusion of jaw, enlarged tongue (macroglossia), enlarged hands and feet, carpal tunnel etc

Question 18

GH deficiency in adults

Answer 18

usually pituitary problems. increased interstitial fat, reduced strength and bone loss. anxiety, depression.
increases clotting factors, LDL, and insulin resistance. can lead to cardiovascular disease. decreases HDL

treat with rhGH.

Question 19

what is GH therapy approved for?

Answer 19

GH deficiency, idiopathic short stature, turner syndrome, prader-willi syndrome, chronic renal insufficiency, small for gestational age

Question 20

short stature in turner syndrome

Answer 20

insuffiency of SHOX gene. SHOX protein is concentrated in the hypertrophic region of the growth plate zone during childhood. without it, you have slower velocity during childhood, and a scant pubertal growth spurt