growth axis Flashcards
how is GH released? and what underlies the mechanism?
in pulastile manner, perhaps due to somatostatin
what is somatostain coupled to, and how does it reduce GH secretion?
Coupled to Gai- this is linked to PLC which negatively regulates adenylate cyclase, this reduces GH secretion (and not synthesis) because it reduces the effect of GHRH within the somatotrops
what is GHRH coupled to?
this is coupled to Gas - this is linked to cAMP-CREB - PKA pathway - which regulates gene transcription and causes somatotroph cell proliferation
how is responsible for the pubertal spurt in GH?
estrogens and androgens and this is because the synthesise the anterior pituitary to GHRH
explain how the GH receptor work?
The GH receptor is part of the cytokine receptor family. receptor has a single transmembrane portion, and is found in inactivated dimer state (if no ligand is bound), once ligand binds autophosphorylation of the JAK-2 residues occurs, and this recruits STAT (via its tyrosine kinase activity). STAT causes a change in gene transcription, producing IGF-1 and SOCS (this inhibits and terminates this signalling cascade)
how does GH cause insulin resistance?
GH increases lipolysis and this reduces glucose metabolism. it also seems that SOC-1 and SOC-3 inhibit PI-3K directly- so insulin resistance can also be intracellular mediated
how does GH cause insulin resistance?
GH increases lipolysis and this reduces glucose metabolism. it also seems that SOC-1 and SOC-3 inhibit PI-3K directly- so insulin resistance can also be intracellular mediated
what is the gene GH-N associated with?
this is associated with post-natal growth - they’re expressed in the anterior pituitary
what is the gene GH-V and CS associated with?
this is associated with in utero growth, they’re expressed in the synctiotrophoblast
what are the metabolic actions of GH?
synergies with cortisol and antagonises the effect of insulin and this means it reduces glucose metabolism (hence diabtogenic when in excess)
increases lipolysis and NEFA release, this is enhanced in fasting states (Contributes to insulin resistance)
increase in protein synthesis
what are the indirect effects of GH mediated through IGF-1?
growth promotion, clonal expansion of tissue and growth of bone, soft tissue and viscera
what is the fusion of the growth plates dependant on?
oestrogen
what is the most important enzyme required for growth plate closure?
aromatise which converts androgens to oestrogens
when do we start requiring GH for growth?
after the 1st year, and this is because growth during the 1st year is dependant on the nutritional status, GH receptors do not start appearing until 7 months
what is the effect of oestrogen and progesterone on GH
They increase its relaase by synthesising the AP to GHRH
what is the effect of thyroid hormone on GH?
Increases its release, because it directly promotes its transciprtion
what is the affect of the adrenal gland on GH?
the adrenal gland releases hormones that inhibit GH (cortisol)
when is oxandrolone used?
this is used in delayed puberty, it is a weak androgen which is not aromatised (therefore does not cause plate fusion) just increase amount of GH release
not used in females, because risks masculinisation
what is the provocative test?
this is when insulin is given, this suppresses glucose, therefore, we’d expect an increase in the level of GH
this is known as the insulin tolerance test- very helpful in identifying classical idiopathic GH hormone deficiency
what is the suppressor test?
this is when glucose is given, and this suppresses GH- if there is a timor secreting GH no decline will be seen in GH levels
describe GH secretion?
secreted in a pulsatile fashion, with peaks during periods 2 and 3 of the sleep cycle.
people with delayed sleep, have delayed peaks in their GH secretion
what is PCOS?
This is the most common caused of decreased or absent menstruation with detectable oestrogen levels
what are the classical observations made in pseudo-hypoparathryodism
exessivel short 4th metacarpal, severe mental retardation and marked kyphosis
what are the classical observation in Junvenile Cushing’s
central adiposity, plethoric face, abdominal striae
