Somatotrolic (Recombinant Human Growth Hormone)
RegulationSecretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH or somatocrinin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL. Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages.Surges of secretion during the day occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL.Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL.
A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day.Sleep deprivation generally suppresses GH release, particularly after early adulthood.
Stimulators of growth hormone (GH) secretion include:
- peptide hormones
- GHRH (somatocrinin) through binding to the growth hormone-releasing hormone receptor (GHRHR)
- ghrelin through binding to growth hormone secretagogue receptors (GHSR)
- sex hormones
- increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
- clonidine and L-DOPA by stimulating GHRH release
- α4β2 nicotinic agonists, including nicotine, which also act synergistically with clonidine.
- hypoglycemia, arginine and propranolol by inhibiting somatostatin release
- deep sleep
- niacin as nicotinic acid (Vitamin B3)
- vigorous exercise
Inhibitors of GH secretion include:
- GHIH (somatostatin) from the periventricular nucleus
- circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)
In addition to control by endogenous and stimulus processes, a number of foreign compounds (xenobiotics such as drugs and endocrine disruptors) are known to influence GH secretion and function.