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Growth hormone (GH) is a peptide hormone. It stimulates growth and cell reproduction in humans and other animals. It is a 191-amino acid, single-chainpolypeptide hormone that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. Somatotrophinrefers to the growth hormone produced natively in animals, whereas the term somatropin refers to growth hormone produced by recombinant DNA technology,[1]and is abbreviated “rhGH” in humans.
Growth hormone is used clinically to treat children’s growth disorders and adult growth hormone deficiency. In recent years, replacement therapies with human growth hormones (HGH) have become popular in the battle against aging. Reported effects include decreased body fat, increased muscle mass, increased bone density, increased energy levels, improved skin tone and texture, and improved immune system function. At this time HGH is still considered a very complex hormone and many of its functions are still unknown.[2]
In its role as an anabolic agent, HGH has been used by competitors in sports since the 1970s, and it has been banned by the IOC and NCAA. Traditional urineanalysis could not detect doping with HGH, so the ban was unenforceable until the early 2000s, when blood tests that could distinguish between natural and artificial HGH were developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece primarily targeted HGH.
The 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 andprimate growth hormones have significant effects in humans.
Several molecular isoforms of GH circulate in the plasma. Much of the growth hormone in the circulation is bound to a protein (growth hormone-binding protein, GHBP) which is derived from the growth hormone receptor, and an acid labile subunit (ALS).
Regulation
Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone-releasing hormone and somatostatin) into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. However, although the balance of these stimulating and inhibiting peptides determines GH release, this balance is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors of GH secretion (e.g., Free fatty acids)[3]
Stimulators of GH secretion include:
- peptide hormones
- sex hormones[6]
- clonidine and L-DOPA by stimulating GHRH release[7]
- hypoglycaemia, arginine[8] and propranolol by inhibiting somatostatin release[7]
Inhibitors of GH secretion include:
- somatostatin from the periventricular nucleus [12]
- circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)[2]
- hyperglycemia[7]
- glucocorticoids[13]
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.[14]
Secretion patterns
HGH is synthesized and secreted from the anterior pituitary gland in a pulsatile manner throughout the day; surges of secretion occur at 3- to 5-hour intervals.[2] The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL.[15] The largest and most predictable of these GH peaks occurs about an hour after onset of sleep.[16] Otherwise there is wide variation between days and individuals. Nearly fifty percent of HGH secretion occurs during the third and fourth REM sleep stages. [17] Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.[16] 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.[18][19]
A number of factors are known to affect HGH secretion, such as age, gender, diet, exercise, stress, and other hormones.[2] Young adolescents secrete HGH at the rate of about 700 μg/day, while healthy adults secrete HGH at the rate of about 400 μg/day
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