Growth Hormone (GH)
It either directly act on the cell or it acts by producing Stomatimedins (produced by Liver).
Family: prolactin, hPL and GH. They are peptides.
GH act directly or indirectly ( stimulate liver to produce stomatimedins )
Mechanism of Action:
It act on 1-pass receptors present on cell membrane.
1)On stimulus the receptors DiMers are formed.
2)Dimerization of the receptors activates Janus kinases.
3) phosphorylated janus kinases (JAK) activate STAT ( signal transductor and activator of transcription) by phosphorylation and DiMer of STAT is formed. And this STAT then travels to the nucleus and activates the transcription.
Second method of action: is alteration of metabolism of cell by phosphorylation and de-phosphorylation of different proteins by STAT.
Note:
Growth hormone has less affinity to bind with plasma proteins that why its half life is 20 minutes but stomatimedins has high affinity to buy with plasma protein that's why it has half life of 24 hours.
Dwarfism of African pygmies (Lorain dwarfism) is due to low level of somatomedin but growth hormone level is normal.
Function of GH:
Increase lipolysis ( catabolism of lipid) decrease inappropriate fat in body.
Increase protein mass (increase lean body mass, anabolism of protein)
Proteins & GH:
Increase Amino acid uptake
Increase transcription
Decrease catabolism of protein
Lipid & GH:
GH stimulates "hormone sensitive lipase" in the adipocytes.which increases the lipolysis of fat and this results in increase in free fatty acids.
Free fatty acids can be used as energy by breaking down by Beta Oxidation to acetyl CoA. And extra acetyl CoA can be transformed into ketone bodies in liver.
Glucose and GH
It decreases the uptake of glucose by muscle and adipocytes thus creating diabetoganic action.( Anti insulin) Now it is believed that high level of fatty acids in blood cause insulin resistance by inhibiting the receptors.
Bone and GH
Growth plates become more active. It increases the Length and width of bone.
After adolescence, high level of GH causes membranous bones to increase in width,. This condition is called acromegaly.
Somatomedin C is also known as insulin like growth factor 1
Regulation of GH
1)High somatomedin give positive feedback to cells in hypothalamus secreting somatostatin.
2) high GH give positive feedback to cells in hypothalamus secreting somatostatin.
3) somatomedin also give negative feedback to Anterior pituitary cells producing GH.
4) GH is secreted in pulsating manner. And secretion is high during Sleep
5) in stressful conditions GH secretion increase.
6) low free fatty acids .. increase secretion
7) low glucose level .. increase secretion
8) fasting/ starvation_ increase secretion
9) excercise increase growth hormone
10) obesity .. GH will go down.
11) beta adrenergic agonists also reduce GH.
12) aging. GH reduce
13) GH level decrease during pregnancy to provide glucose and fatty acids to fetus.
Conditions in which GH level are low:
Panhypopituitarism ( in adult);
Sheehan's syndrome ( in post partum females)
Tumors in : craniopharyngioma , chromophobes tumor.
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