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StructureThe major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species, only human and Old World monkey growth hormones have significant effects on the human growth hormone receptor.Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. This variant has not been identified, but it has been suggested to coincide with a 22 kDa glycosylated variant of 23 kDa identified in the pituitary gland. Furthermore, these variants circulate partially bound to a protein (growth hormone-binding protein, GHBP), which is the truncated part of the growth hormone receptor, and an acid-labile subunit (ALS).
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.[3] 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)[21]
  •     sex hormones
  •     increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
  •     estrogen
  •     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)
  •     fasting
  •     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)
  •     hyperglycemia
  •     glucocorticoids
  •     dihydrotestosterone

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.