Growth Hormone and Somatomedin Flashcards

1
Q

which hypothalamic hormones regulate the pulsatile secretion of GH

A

GHRH

somatostatin (also called somatotropin release-inhibiting factor, SRIF)

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2
Q

after GHRH interacts with its membrane receptor…

A

increases cAMP and Ca2+ levels in the cell

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3
Q

negative feedback loop on GH secretion

A

insulin-like growth factor-1 (IGF-1) that is released from liver and other tissues….

inhibits release of GH from pituitary gland

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4
Q

What stimulates the secretion of GHRH from the hypothalamus

A

sleep, stress, amino acid rich meal

leads to increase GH from pituitary gland

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5
Q

short term vs long term effects of GHRH on the somatotrophs

A

short = increased release of stored GH

long = increased transcription of the GH gene
–> activates the pituitary gland transcription factor (Pit1)

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6
Q

Thyroid hormone and cortisol effect on GH

A

synergistically enhance transcription of GH gene

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7
Q

what stimulates release of somatostatin from the hypothalamus

A

somatomedin (IGF) and GH

leads to decreased release of GH from pituitary gland

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8
Q

somatomedin regulation on GH release

A

(+) somatostatin release from hypothalamus –> less GH

and

directly (-) GH release at pituitary gland by interacting with receptor and decreasing cAMP and Cs2+

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9
Q

on the balance, GH can partially be considered what kind of hormone

A

diabetogenic

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10
Q

effects downstream of high protein intake…

A

(+) GH and (+) insulin –> caloric storage (+/-)

(+) somatomedin –> (+) protein synthesis, (+) growth

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11
Q

effects downstream of carbohydrate intake…

A

(-) GH with (+) insulin –> (+) caloric storage

(+/-) somatomedin –> (+/-) protein synthesis and growth

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12
Q

effects downstream of fasting

A

(+) GH with (-) insulin –> caloric mobilization

(-) somatomedin –> (-) protein synthesis and growth

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13
Q

effects of GH on the liver

A

increase in the following…

  • RNA and protein synthesis
  • gluconeogenesis
  • synthesis and secretion of IGFBPs and IGFs
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14
Q

effects of GH and IGFs on muscle

A

(-) glucose uptake

(+) amino acid uptake

(+) protein synthesis

(+) lean body mass

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15
Q

effects of GH on adipose tissue

A

(-) glucose uptake

(+) lipolysis

(-) adiposity

***IGFs do not effect adipose tissue like they do muscle

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16
Q

GH and IGF effects on extrahepatic tissues

A

increases in the following

protein, RNA, and DNA synthesis

cell and organ size

organ function

17
Q

GH and IGF effects on chondrocytes

A

increases in the following…

amino acid uptake
RNA/DNA/protein synthesis
collagen
chondroitin sulfate
cell size and number
linear growth
18
Q

fetal GH detection

A

detectable in the fetal serum

concentration increases rapidly and peaks at 100-150ug/L at about 20th week

19
Q

GH concentration in premature babies

A

higher than normal babies

levels decrease to about 30 and continue to fall during the early postnatal months

20
Q

somatostatin effect on the function of GHRH

A

blocks GHRH stimulation on the pituitary gland by a non competitive means

interacts with own membrane receptor to decrease cAMP and Ca2+

also lowers frequency and amplitude of GHRH release from hypothalamus

21
Q

sharp drop in glucose and fFAs –>

A

increase GH

22
Q

obesity and GH

A

reduces GH responses to all stimuli

including GHRH

23
Q

nocturnal surge of GH

A

1-2 hours after onset of deep sleep (not REM)

REM lowers GH

24
Q

mechanism of GH action

A
  1. attaches to 2 docking sites on receptor
  2. receptor dimerizes
  3. intracellular domains then dock and activate JAK-STAT tyrosine kinase pathway
  4. these kinases phosphorylate STAT transcription factor proteins
  5. which activate GH-dependent gene transcription and expression –> modulation of IGFs, IGFBPs and other molecules expression
25
Q

what organ makes most of the IGFs

A

liver

26
Q

circulation of IGFs

A

bound to a number of large binding proteins that regulate their availability to tissues

27
Q

GH deficient patients level of IGFs

A

lowered

especially IGF-1

28
Q

what stimulates IGF production during fetal growth

A

a GH variant present in the placenta

the IGF-2 and its receptor are expressed very early in fetal development

29
Q

the progression of pubertal growth correlates with the plasma increases in what

A

IGF-1

30
Q

IGF and GH levels in fasting state

A

GH is elevated but IGFs are lowered

therefore,

must be other factors regulating IGF production…

soooooo

high GH levels probably result from a negative feedback mechanism caused by low IGFs

31
Q

cortisol and estrogens on IGF production

A

lower it

any hormones that antagonizes GH action will lower IGFs too

32
Q

GH effect on chondrocytes

A

stimulates differentiation of prechondrocytes into chondrocytes which then secrete IGF-1

which stimulates clonal expansion and maturation of chondrocytes

33
Q

insulin antagonistic effect of GH helpes prevent what

A

hypoglycemia

34
Q

insulin and GH and IGF levels after fasting

A

insulin falls

GH rises

but IGF still fall

35
Q

why is GH increase during fasting good?

A

contributes to enhanced lipolysis and decreases peripheral tissue glucose use

36
Q

Prolactin struture compared to GH

A

very much homologous except for extra 3rd disulfide bonded loop

37
Q

how is prolactin made

A

made as a preprohormone

signal peptide is cleaved in ER membrane

temporarily N-glycosylated in ER then taken off in Golgi

38
Q

secretion of prolactin regulation

A

inhibited by prolactin inhibitory factors (PIFs) from hypothalamus –> primarily dopamine

others include somatostatin and alternatively spliced GnRH

Thyroid releasing hormone (TRH) is a major stimulator of prolactin