Human growth hormone or hGH
The three-dimensional structure is stabilized by two disulfide bridges four helical structures. The position of the helices and the overall three-dimensional structure of this hormone are important for receptor binding. The hormone shares structural homologies with prolactin and human chorionic somatomammotropin (hCS). HCS is a growth hormone variant synthesized exclusively in the placenta. There is a cluster of five genes from which these polypeptide hormones may be synthesized but normally only one gene expressed tissue-specifically. Binding of the tissue-specific transcription factor Pit-1 to the promoter region of the growth hormone gene results in only one form of growth hormone that are secreted by the anterior pituitary gland.
Before recombinant technology was available, the only source of hGH was human cadavers, but the contamination that led to Creutzfeldt–Jakob disease made this form of treatment obsolete. During the late 1980s, recombinant hGH (rhGH) was developed through genetic engineering. Recombinant hGH has been used with good results in the treatment of patients with hGH deficiency allowing bone growth and impacting on the patient’s final stature. This form of hGH has a sequence identical to the naturally occurring 22 kDa hormone.
Some athletes and bodybuilders appear to have used rhGH and claim that it increases lean body mass and decreases fat mass. Besides its anabolic properties hGH also effects carbohydrate and fat metabolism. During sport doping investigations rhGH has been found in swimmers and also in players taking part in other major sports events. International federations and the International Olympic Committee have hGH now on the list of forbidden compounds since 1989.
Human growth hormone is secreted from somatotropic cells in the anterior pituitary gland in a pulsating fashion. Two hypothalamic peptides, growth hormone releasing hormone, which stimulates hGH secretion, and somatostatin, which inhibits hGH secretion by back regulation, regulate its secretion.
hGH binds to specific receptors present throughout the whole body and exerts its biological effects on target cells. The secretion of hGH is slightly higher in women than in men. The highest levels are observed at puberty. Secretion decreases with age by approximatelly 14 % per decade. In addition, secretion of the hormone varies with normal physiological and pathological conditions and hGH levels are higher during slow wave sleep and are increased by exercise, stress, fever, fasting and, with increased levels of some amino acids (leucine and arginine). Drugs, such as clonidine, L-dopa and c-hydroxybutyrate, increase its secretion, as do androgens and estrogens. hGH binds to specific membrane receptors found in abundance throughout the body. It has both direct and indirect effects on the tissues. Indirect effects are mediated by IGF-1, generated in the liver in response to GH.
References
Chantalat L, Jones ND, Korber F, Navaza J, Pavlovsky AG; The crystal-structure of wild-type growth-hormone at 2.5 angstrom resolution. Protein Pept.Lett. (1995) 2 p.333.
M Saugy, N Robinson, C Saudan, N Baume, L Avois, P Mangin; Human growth hormone doping in sport. Br J Sports Med 2006;40(Suppl I):i35–i39. doi: 10.1136/bjsm.2006.027573.