Growth hormone , human

Hiunan growth hormone (hGH) is a single chain polypeptide of 191 amino acids, containing two intramolecular disulfide bonds (ref. 8). The monomer molecular weight of hGH is 22,125. HGH is produced by the pituitary gland and is an Important mediator of growth as well as of several other biological activities. 

The structure of the active form or forms of hGH has been the subject of intense investigation and controversy over the years. The determination of the size of hGH in the circulation by size exclusion chromatography has been the subject of a number of reports (for example, ref. 9). Small zone SEC of serum, monitoring the elution of hGH by a radioimmunoassay, has revealed that, under certain circumstances, hGH can elute with an apparent molecular weight greater than the monomer molecular weight. 

For each concentration of hGH, the centroid elution volume was taken as the Inflection point of the leading boundary of the plateau region. The inflection point was determined by locating the point at which the second derivative of the leading boundary curve was equal to zero. A plot of the elution volumes as a function of log concentration is shown in figure 2. The elution volumes expected for hGH sionomer and hGH disier, determined by a calibration of the column, are indicated. Clearly, there is no decrease in centroid elution volume with increasing concentration as would be expected for a system in which a rapid equilibrium existed between different size 

It was known as early as the 1920s that the pituitary gland contained a factor that could promote growth, but not until 1956 (1) was the factor isolated. hGH is extremely abundant in the pituitary, representing as much as 10% of this gland s dry weight, or 8 mg of hormone per gland (2). 

Two weU-known pathological conditions are the result of an excess or a deficiency of this hormone. The condition in which the body produces an excess of hGH is known as acromegaly or giantism. The condition in which too Httle is produced is dwarfism. 

Purified hGH is a white amorphous powder in its lyophilized form. It is readily soluble (concentrations 10 mg/mL) in dilute aqueous buffers at pH values above 7.2. The isoelectric point is 5.2 (3) and the generally accepted value for the extinction coefficient at 280 nm is 17,700 (Af-cm) (4), 

Kirk-Othmer Encyclopedia of Chemical Technology (4th Edition) 

Methionyl hGH. The first form of hGH to be produced through recombinant DNA technology was actually a derivative of hGH having one additional methionine residue at its N-terminus (11). Although technology has advanced to the stage where natural sequence hGH can easily be produced, as of this writing this derivative, referred to as methionyl hGH, is stiU produced commercially. 

Mature hGH contains 191 amino acid residues and displays a molecular mass of 22 kDa. It also contains two characteristic intrachain disulfide linkages. hGH mRNA can also undergo alternate splicing, yielding a shortened GH molecule (20 kDa), which appears to display biological activities indistinguishable from the 22 kDa species. 

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COLORANTSFORFOOD,DRUGS,COSTffiTICSANDTffiDICALDEVICES] pol6) hGH See Human growth hormone. 

Therapeutics. Therapeutic materials represent a class of polypeptides that are a low volume, high value product. The production system need not be very efficient but the quaHty of the recombinant protein has to be extremely pure (33,34). Thus high cost mammalian production systems can be tolerated. However, some of the therapeutic proteins such as insulin, human growth hormone, interleukins, interferon, and streptokinase are produced microbially. 

Table 3. Effects of Ovine Somatotropin (oST) and Human Growth Hormone-Releasing Factor (hGRF) on Growth and Composition of Gain in Lambs ...

Anterior pituitary hormones, Anterior pituitary-like hormones. Posterior pituitary hormones. Human growth hormone. 

Fig. 1. Primary stmcmre of the human growth hormone family of proteins. GH-N = pituitary GH GH-V = placental GH variant ...

Human growth hormone is a single polypeptide chain of 191 amino acids (qv) having two disulfide bonds, one between Cys-53 and Cys-165, forming a large loop in the molecule, and the other between Cys-182 and Cys-189, forming a small loop near the C-terminus. The stmcture of hGH is shown in Figure 1 molecular mass is 22,125 the empirical formula is C qH 29N 262 300 7 ... 

Human growth hormone is a very complex molecule biologically. Several diverse biological activities such as anaboHc, insulin-like, diabetogenic, and lactogenic activities have been ascribed to hGH, which also appears to promote water and salt retention. An in-depth discussion of these activities may be found in several excellent reviews available in the Hterature (34—36). 

Human growth hormone, used as a human pharmaceutical, is approved for only one indication in the United States, treatment of growth failure owing to hGH deficiency, a condition known as pituitary dwarfism. However, clinical trials are under way to test its efficacy in Turner s syndrome, bums, wound healing, cachexia, osteoporosis, constitutional growth delay, aging, malnutrition, and obesity. 

Human growth hormone was originally manufactured by isolation of the natural product from human pituitaries and subsequent purification of the protein. Since 1985, manufacture of hGH has been almost exclusively by recombinant DNA technology. 

Human growth hormone is one of the largest selling therapeutic proteins produced by recombinant DNA technology. Annual worldwide sales increased from 130,000,000 in 1987 to 575,000,000 in 1992 (47). Upon approval of additional indications, the sales of hGH are expected to increase even more. 

J. L. Kostyo, iu L. E. Underwood, ed.. Human Growth Hormone Progress and Challenges, Marcel Dekker, New York 1988, p. 63. 

Reports have appeared in the Hterature of the use of human growth hormone in older men. It has been proposed that a reduction in growth hormone in old age is responsible for increased adipose tissue, loss of lean body mass, and thinning of skin. Current studies conducted on older men indicate the hormone reverses these effects. In the parameters studied the patients resembled those of persons 10 —20 years younger (70). 

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