Physiology of Growth Hormone

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Type 2 IGF Receptor

IGF receptor that binds IGF2 with high affinity and binds IGF1 with low affinity, it is the clearance receptor for IGF2

Type 1 IGF receptor

IGF receptor that has an active second messenger signaling, TYR kinase phosphorylation, has multiple pathways (SH2 pathway, PI3K/PIP2 pathway)

Type 1 IGF Receptor

IGF receptor that is a heterotetramer, binds IGF1 and IGF2 with high affinity, structurally almost identical to insulin receptor, present in almost all tissue

Type 2 IGF receptor

IGF receptor that is mostly inactive with no downstream signaling and is therefore presumed to be a clearance receptor

IGFBP-3

IGFBP that is a major carrier in circulation and stimulates endocrine function

IGFBP-4

IGFBP whose endocrine function inhibits IGF action causing serum concentrations to be low

IGFBP-6

IGFBP whose endocrine function is to bind IGF2 and inhibits its action

IGFBP-5

IGFBP whose paracrine function is as a growth factor in bone matrix

IGFBP-4

IGFBP whose paracrine function is as a growth factor in tissue specific expression, locally regulates IGF

IGFBP-2 and 6

IGFBP whose paracrine function is as growth factors in CSF

IGFBP-3

IGFBP whose paracrine function is as growth factors in follicular fluid

IGFBP-1

IGFBP whose paracrine function is growth factors in amniotic fluid

1. Hyperglcemia 2. Elevated levels of insulin 3. Elevated levels of free fatty acids

What are factors that inhibit growth hormone secretion?

1. hypoglycemia 2. High levels of amino acids (especially during starvation) 3. Stress

What are factors that stimulate GH secretion

1. Growth hormone releasing hormone (GHRH) 2. Somatostatin (SRIF)

What are the two hormones that regulate growth hormone secretion?

strenuous exercise and fasting

When does episodic release of growth hormone occur?

long loop feedback

Which feedback loop does the IGF use?

short loop feedback

Which feedback loop does the growth hormone use?

growth hormone

binds with the GH receptor on hepatocytes to stimulate the secretion of the insulin like growth factors

growth hormone

binds with the membrane bound GH receptor on muscle and adipose to stimulate growth

gigantism

caused by excessive and unregulated growth during childhood, usually by pre-closure of epiphyses in the pituitary

IGFBP proteases

cleave IGFBP into active forms

IGF Binding Proteins (IGFBP)

dynamic proteins that transport the IGFs and also exhibit some endocrine effects

acromegaly

excessive secretion of growth hormone during adulthood, usually by post-closure of epiphyses

IGFBP

extends IGF half-life and regulate availability of IGF

growth hormone binding protein (GHBP)

extends the half-life of the serum growth hormone

pituitary dwarfism

growth hormone deficiency during childhood, cause by pre-closure of epiphyses. This condition is treatable

somatostatin

hormone that inhibits the release of the growth hormone

growth hormone

in the adipose tissue stimulates lipolysis and inhibits glucose uptake

IGF

in the chrondrocytes it stimulates amino acid uptake, protein synthesis, RNA synthesis, DNA synthesis, collagen production, chrondroitin sulfate, hyperplasia, hypertrophy

growth hormone

in the liver stimulates protein synthesis, gluconeogenesis, glycogenolysis, and IGFS. It inhibits Glycogenesis

IGF

in the muscle stimulates protein synthesis, amino acid uptake, and glucose uptake

growth hormone

in the muscle stimulates protein synthesis, amino acid uptake, glycogenolyis. It inhibits glucose uptake

growth hormone

increases lipolysis in adipose tissue, reduces glucose uptake in muscles, and increases hepatic gluconeogenesis

IGF2 (Somatomedin A)

insulin growth factor important for fetal/placental growth and development. Highest concentration of circulating IGF in adults, primarily cleared from circulation by binding with IGF Type 2 receptor

IGF1 (Somatomedin C)

insulin growth factor that is primary functional hormone after birth, change in it parallel changes in growth hormone from birth to death. Lethal if knockout in transgenic mice

IGF-1

insulin growth factor that is produced in the brain, muscle and bone

growth hormone

stimulates the JAK and the STAT or MAPK pathways

Growth hormone

stimulates the liver to secrete IGF

Growth hormone

191 amino acid polypeptide with 2 disulfide bonds

IGF

mediates the effects of Growth Hormone

growth hormone binding protein

produced by metalloproteolytic cleavage (especially in adipose tissue) of the GH receptor extracellular domain

GHBP

protects growth hormone from degradation

Insulin receptor

receptor that binds IGF1 at lower affinity than insulin

Hybrid IGF-Insulin Receptors

receptors that have been proposed as a potential source and/or as a contributing factor for receptor-mediated insulin resistance

growth hormone

regulates growth, works in concert with insulin life growth factors (IGFs) to maintain and stimulate growth

growth hormone

released before eating to stimulate cellular metabolism, works in concert with IGFS and insulin to utilize glucose

IGF (1 and 2)

released from the liver to regulate maintenance and growth of tissues throughout the body

...

the secretion of growth hormone peaks during puberty and then slowly declines during adulthood


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