Human+Growth+Hormone

=​Human Growth Hormone=

General information
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Nutropin (Genentech); Genotropin (Pfizer); Humatrope (Lilly); Norditropin (Novo Nordisk); Saizen (EMD Serono) ||
 * ~ Product Name || Recombinant Human growth hormone (rhGH)
 * ~ Inventors || Peter H. Seeburg ||
 * ~ Patent holders || Genentech, Inc. ||
 * ~ Area of Application || Health Care (Endocrinology) ||
 * ~ Market Size || US$2.7billion (2007) ||

Human growth hormone (hGH) is a protein with 191 amino acids (MW = 22125 Da) which folds into a four-helix bundle structure with two disulfide bridges. It’s naturally produced in the pituitary gland and plays a central role in the growth process and maturation from child to adulthood. It also regulates a number of metabolic and physiological processes throughout life. GH deficiency occurs when the pituitary gland is unable to produce or release sufficient amounts of hGH.

History

 * 1) 1963 to 1985 - cadaver-derived hGH (pre-recombinant DNA technology)
 * 2) 1985 to present - Recombinant hGH

1. The hGH was purified from the pituitary glands of human cadavers, being 7700 children treated in the US only, and many of them grew significantly. However, it was found that a significant amount of men treated with the cadaver-derived hGH had developed Creutzfeldt-Jakob disease (a very rare and fatal degenerative brain disease), which consequently lead to the cancelation of the procedure. 2. Genentech successfully cloned the human growth hormone gene in //E.coli// and in 1985 they received approval from FDA to market hGH, with the brand name protropin, indicated only for the long-term treatment of children with GH deficiency. This was their second pharmaceutical obtained with the recombinant DNA technology (after insulin) and the first one to be manufactured and marketed by them (first biotechnology company to do so). The use of //E.coli// is viable because hGH is a nonglycosylated protein and therefore a prokaryotic expression system is preferred, although having difficulties associated with purification from endogenous contaminating proteins of the host.

Recent Advances
In 1994, Genentech changed the brand name to Nutropin, due to the discovery of new applications for hGH, namely the treatment of growth failure associated with chronic renal insufficiency prior to kidney transplantation, short stature associated with Turner syndrome, and long-term treatment of idiopathic short stature. Since then, the FDA has been approving new applications for rhGH produced by many companies, for instance Genotropin from Pfizer is the only rhGH approved for the treatment of growth failure in children with Prader-Willi syndrome, which consequently revitalized the worldwide market. More recently, EMD Serono found a new method using a different expression system, specifically a mammalian cell line (mouse C127) also cloned with the hGH gene, which allows the protein to be secreted directly through the cell membrane into the cell culture medium, with the correct 3-dimensional configuration, for collection and purification.

Some of the applications for rhGH are:
 * Growth hormone deficiency
 * Short stature associated with Turner syndrome
 * Idiopathic short stature
 * Children born small for gestacional age
 * Growth failure associated with chronic renalinsufficiency prior to kidney transplantation
 * Growth failure in children with Prader-Willi syndrome
 * Short stature homeobox-containing gene (SHOX) deficiency
 * GH hormone deficiency in adults due to brain surgery, radiation therapy, trauma or diseases of the pituitary gland or the hypothalamus