Anterior Pituitary Flashcards
what is the most abundant cell type anterior pituitary
somatotropes
what hormones make up glycoprotein family
FSH
LH
TSH
hCG (human chorionic gonadotropin)- placental glycoprotein hormone
glycoprotein family (composition)
two subunits held together by non-covalent bonds
alpha subunit identical in all
beta subunit unique for each
member of glycoprotein family use what signaling pathway
cyclic AMP signaling pathway (Gs)
what hormones are members of the somatomammotropin family
GH
PRL
hGH-v (placental GH)
hCS (chorionic somatomammotropin)/ hPL (placental lactogen)
member of the somatomammotropin family have what type of protein structure
single chain proteins containing intrachain disulfide bridges
2 for GH and hCS
3 for PRL
what hormones are in the proopiomelanocortin family
ACTH
about half the GH in circulation is what
bound to GH binding protein
GH binding protein has the same molecular structure as what
external portion of GH receptor (formed by cleavage of receptor)
GH (direct actions)
IGF-1 production
lipolysis by adipocytes
amino acid uptake and protein synthesis by liver
what induces most of the growth promoting factors of GH
IGF-1
GH has what type of metabolic effects with respect to carbohydrate and lipid metabolism
“diabetogenic” effects
net result of the metabolic actions of GH
promote fat mobilization and utilization (lipolysis)
conserve blood carbohydrate
how does GH conserve blood carbohydrate
inhibits glucose uptake by skeletal muscle and adipose tissue
decreases sensitivity of these tissues to insulin
GH has what effect on circulating free fatty acid levels
increases them
in a hypopituitary subject GH administration does what (in regards to skeletal growth)
increases chondrocyte proliferation in cartilage growth plate
proliferation of what is responsible for bone length growth
chondrocyte
proliferation of what is responsible for bone width growth
osteoblastic progenitor cells
GH has what net effect on soft tissue
to increase lean body mass
how does GH increase lean body mass
stimulates uptake of amino acids and protein synthesis and inhibits proteolysis in skeletal muscle and other GH-responsive tissues
in the presence of GH what happens to blood urea and urinary nitrogen excretion
decreases as amino acids are converted to proteins
exogenous GH does what to body fat
reduces body fat by mobilizing fat stores and decreasing fat deposition
GH increases the mass of what organs
liver and spleen
GH receptor is what kind of receptor and works via what pathway
cytokine receptor family
JAK/STAT pathway
GH receptor has what kind of catalytic activity
no intrinsic catalytic activity instead intracellular kinase is tightly bound to cytoplasmic domain
janus kinase family (JAK) is what
receptor associated tyrosine kinase
GH binding to receptor does what
induces receptor dimerization
GH has how many binding sites and why
2 in order to bind 2 different receptors and cause dimerization
receptro dimerization of GH receptor allows for what
2 JAKs to come into close enough contact to phosphorylate each other
phosphorylated JAKs on the GH receptor do what
phosphorylate the GH receptor
how does STAT get phosphorylated
dock to phosphotyrosine residues on GH receptor ad JAK phosphorylates them
Phosphorylated STAT proteins do what
form dimers and migrate to nucleus where they activate gene transcription
JAK 2 allows GH to what (in terms of signaling pathways)
active additional intracellular signaling pathways b/c JAK 2 phosphorylates more than one signaling protein
local production of IGF-1 is important for what
mediating many of the action of GH
what expresses receptors for both GH and IGF-1
chondrocytes in epiphyseal plate
circulating IGF-1 is tightly bound to what
IGF binding proteins (IGFBP)
IGFBPs (function)
provide circulating reservoir of IGF
increase circulatory half life
modulate bioavailability of IGF
at high concentrations IGF-1 will mimic what
actions of insulin
what IGFBP has highest affinity for IGFs
IGFBP-3
most IGF in blood is transported in a large molecular weight complex composed of what
IGF
IGFBP-3
acid-labile subunit (ALS)
IGF-1’s affinity is greater for IGF receptor or IGFBP?
IGFBP
what happens to IGF-1’s affinity to IGFBP
when IGFBP binds to surface of target cell or is degraded by IGFBP proteases the affinity decreases
the IGF-1 receptor is what type of receptor
receptor tyrosine kinase
growth promoting and mitogenic actions of IGF-1 are done through what pathway
Ras/Map kinase signaling pathway
target cells for IGF
fibroblasts chondrocytes osteoblasts adipocytes muscle cells
name some specific effects of IGFs
stimulation of DNA, RNA and protein synthesis
cell proliferation
insulin-like effects on adipose tissue and muscle
GHRH stimulates what and how
synthesis and release of GH via cAMP and PKA
PKA has what effect on GH and GHRH
induces transcription og GH and GHRH receptor
what inhales the action of GHRH on GH release
ghrelin
somatostatin (what does it do in ratlin to GH)
blocks basal and GHRH-stimulated GH release
somatostatin (how does it work)
Gi
inhibits adenyl cyclase and activated K+ channels to hyper polarize the cell membrane
short feedback of GH secretion
GH inhibits GHRH secretion form hypothalamus and stimulates somatostatin release
long feedback of GH secretion
IGF-1 inhibits GH secretion by working on the pituitary of hypothalamus
in what type of pattern is GH released
secretory pulses in circadian pattern of release
large burst of GH occurs when
1-2 hours after onset of deep sleep
conditions that stimulate GH secretion
exercise
stress
sleep
protein meal or IV infusion with certain amino acids (arginine)
postprandial (insulin induced) hypoglycemia
sex steroids
ghrelin
conditions that inhibit GH secretion
hyperglycemia
elevated levels of free fatty acids
after 48hour fast what would GH and total IGF-1 plasma levels be like
GH significantly elevated
total IGF-1 levels are unchanged
what happens to free IGF-1 after 24 hour fast
decline by 50%
during starvation and protein-calorie malnutrition what happens to circulating GH and IGF-1 levels
GH levels are elevated
circulating IGF-1 levels are decreased
why can GH levels be elevated while IGF-1 levels decreased
hepatic IGF production requires adequate neutron and insulin
when is daily pituitary output of GH highest
adolescent growth spurt
what happens to GH and IGF levels with age
GH decreases steadily after 3rd decade
IGF declines in proportion to GH output
