experimental history of growth hormone
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History of Growth Hormone
The efforts to acquire pituitary GH for the treatment of GH-deficient children started in the mid-1940s. Initial work was on subprimates for nearly a decade. These efforts led to the purification of bovine GH by Li and Evans at the University of California, Berkeley, and Fishman at Yale. And porcine GH was purified by Raben and Westermeyer, at Tufts. But none of these preparations showed a significant biochemical or metabolic activity because the effects of GH is species specific.[1]
Growth hormone (GH) first was isolated from the human pituitary gland in 1956, by both Li and Papkoff, in California, and Raben, in Massachusetts, but its biochemical structure was not elucidated until 1972. In 1958, Raben reported the results of the first trial to show the effects of human GH on growth. By 1960 it was clear that GH-deficient children would benefit from pituitary GH. In 1960, National Pituitary Agency (NPA) was formed to further the goals of coordinating pituitary collection and extraction to support both basic and clinical research.[1,2] Between 1963 and 1985 the NPA supervised almost all of the GH treatment in the United States. And during this period about 7700 children in the United States and 27,000 children worldwide were given GH extracted from human pituitary glands to treat severe Growth hormone deficiency (GHD).[3,4]
By 1985, pituitary GH was in use for nearly 30 years in the United States and Canada, either for research purpose or therapeutically. In 1985, US Food and Drug Administration (US FDA) received reports of four young adults in the United States with the fatal, slow viral (prion-mediated) Creuzfeldt Jacob Disease (CJD), who had been treated with GH from the NPA in the 1960s. The connection was recognized on reviewing data within a few months by FDA and NIH. On April 19, 1985, distribution of pituitary GH was suspended and use of human pituitary GH rapidly ceased. And an exciting and important era in pediatric endocrinology came to an abrupt finish.[5]
Identification of the biochemical structure of GH in 1972 became the catalyst for the development of recombinant DNA-derived human GH, the gene for which was cloned for the first time in 1979. Genentech (San Francisco, California), developed in 1981 the first recombinant human GH (rhGH) by a biosynthetic process. Later, an improved process to develop rhGH was developed called protein secretion technology. Wherein, the vector plasmid is isolated from a strain of E. coli and the DNA strand to be cloned is derived from the appropriate source. Both the plasmid and the required DNA strand are cleaved by restriction enzymes, joined together and then reformed into a circular structure. The recombinant plasmid is inserted into E. coli, which is then transformed to synthesize the desired protein This is currently the most common method used to synthesize rhGH, known generically as somatotropin. Discontinuation of human cadaveric GH led to rapid US Food and Drug Administration (FDA) approval of Genentech's synthetic methionyl GH, which was introduced in the United States in 1985 for the therapy of severe childhood GHD.[6,7]
Earlier to the discovery of rhGH, the GH treatment was reserved for only the most severe cases of GHD and, because of scarce supplies. With the development of rhGH, an unlimited commercial source became available, allowing for an ever-growing list of FDA-approved indications for GH use in non–GH-deficient children and for additional indications in adults.