Recombinant human GH

U.S.A., in lactating dairy cattie to increase milk production. EH Lilly and Company, The Upjohn Company, and American Cyanamid Company also have interests in the commercial appHcation of recombinant bovine GH. Recombinant porcine GH [9061-23-8] preparations from several companies, eg. The Upjohn Company, Smith Kline Beecham Animal Health, Pitman-Moore, Inc., Monsanto Company, and American Cyanamid Company, are being evaluated for commercial use. Recombinant human GH for clinical use is marketed under such names as Protropin (Genentech), Umatrope (EH Lilly), Genotropin (Sumitomo), and Somatonorm (Kabi-Vitmm) by a variety of pharmaceutical companies. A listing of additional suppHers is available (2). 

Originally, recombinant human GH (hGH) was expressed with an additional methionine at the N-terminal because all of the amino-acid sequences of E. coli proteins begin with an S-adenosyl methionine. 

Circulating endogenous GH has a half-life of 20-25 minutes and is predominantly cleared by the liver. Recombinant human GH (rhGH) is administered subcutaneously 3-7 times per week. Peak levels occur in 2-4 hours and active blood levels persist for approximately 36 hours. 

Somatropin, recombinant human GH, promotes growth in children with Turner s syndrome (an XO genetic genotype) or chronic renal failure. It also helps combat the AIDS-associated wasting syndrome. Bovine GH promotes milk production in cows. Growth hormone would not be appropriate for the boy with polydipsia and polyuria, which is probably symptomatic of a form of diabetes. The answer is (D). 

Wallace, J.D.,Cuneo,R.C., Bidlingmaier, M.,effli (2001) Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. Journal of Clinical Endocrinology and Metabolism, 86,1731-1737. 

Although most biopharmaceuticals approved to date are intended for human use, a number of products destined for veterinary application have also come on the market. One early such example is that of recombinant bovine GH (Somatotrophin), which was approved in the USA in the early 1990s and used to increase milk yields from dairy cattle. Additional examples of approved veterinary biopharmaceuticals include a range of recombinant vaccines and an interferon-based product (Table 1.7). 

Such effects render IGFs likely therapeutic candidates in treating the various forms of dwarfism caused by a dysfunction in some element of the GH-IGF growth axis. Initial trials show that s.c. administration of recombinant human IGF-I over a 12-month period significantly increases the growth rate of Laron-type dwarfs. 

The situation changed with development of methods for synthesizing proteins by recombinant DNA techniques. In 1979 Goeddel et al. [2,3] published two papers describing the introduction of the genes for human insulin and human GH into Escherichia coli. This was followed by ex-... 

Growth hormone is a 191-amino-acid peptide with two sulfhydryl bridges. Its structure closely resembles that of prolactin. In the past, medicinal GH was isolated from the pituitaries of human cadavers. However, this form of GH was found to be contaminated with prions that could cause Creutzfeldt-Jakob disease. For this reason, it is no longer used. Somatropin, the recombinant form of GH, has a 191-amino acid sequence that is identical with the predominant native form of human GH. 

A small number of children with growth failure have severe IGF-1 deficiency that is not responsive to exogenous GH. Causes include mutations in the GH receptor and development of neutralizing antibodies to GH. In 2005, the FDA approved mecasermin for treatment of severe IGF-1 deficiency that is not responsive to GH. Mecasermin is a complex of recombinant human IGF-1 (rhIGF-1) and recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3). 

Mecasermin Recombinant form of IGF-1 that stimulates IGF-1 receptors Restores normal growth and metabolic IGF-1 effects in individuals with IGF-1 deficiency Replacement in IGF-1 deficiency that is not responsive to exogenous GH SC injection 2 x/d also contains recombinant human IGF-binding protein-3, which prolongs the half-life of the rIGF-1 Toxicity Hypoglycemia, intracranial hypertension, increased liver enzymes... 

Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. J Clin Endocrinol Metab 1995 80(l) 122-9. 

Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon HR 3rd, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 1999 84(11) 3877—85. 

Wolfgang GH, McCabe RD, Johnson DE. Toxicity of subcutaneously administered recombinant human interleukin-2 in rats. Toxicol Sci 1998 42(l) 57-63. 

GH assays now use mouse monoclonal antibodies, and some of these assays are able to discriminate GH variants. Most procedures use recombinant-derived GH for labeling with a tracer and calibration material. The latter is usually prepared gravimetricaUy and verified by comparison with an international reference preparation (IRP), such as the World Health Organization s (WHO s) international standard, IRP 80/505 human growth hormone recombinant (hGHr), which has a potency of 3.3IU/mg of r-hGH, or other standard preparations, such as WHO IRP 66/217 or 88/624. The assay diluent, however, can vary considerably from one assay to another and is a potential source of bias some commercial kits use phosphate-buffered saline, and others use horse, calf, or human serum. 

Growth impairment also may be associated with elevated GH levels and GH resistance, most frequently secondary to mutations in the GH receptor (Laron dwarfism). These patients can be treated effectively with subcutaneous administration of recombinant human IGF-1 (increlex, IPLEX). Although this therapy clearly is beneficial in promoting growth, the optimal regimen remains to be established. 

---