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Human growth hormone hgh (human growth hormone) is secreted by the anterior pituitary gland (adenohypophysis).
From the application of human pituitary growth hormone in 1958 to today's synthesis by genetic engineering technology, growth hormone has experienced the following development processes:
The first stage
The first generation of growth hormone (1950s-1970s) is also called human pituitary derived growth hormone.
It is the first growth hormone used clinically. It was successfully extracted from human pituitary by Raben in 1958, and then began to be used in the treatment of childhood dwarfism.
The disadvantages of this generation of growth hormone are:
1. The source is limited, the output is scarce, and the use process of patients often fails to achieve the expected increase effect due to insufficient dosage;
2. Human pituitary contains growth hormone with various molecular weights (mainly 22 kDa, 20 kDa, and a small amount of 5kd). 22 kDa accounts for 70% ~ 75% of pituitary hGH and 20 kDa accounts for 5% ~ 10% (its affinity with receptor is weak).
Therefore, the content of 22 kDa GH in the product is not 100%, the relative purity is low, and more antibodies are produced.
3. Susceptible to hGH donor virus contamination. In the subsequent treatment, Creutzfeldt Jakob disease (a degenerative neurological disease) was continuously reported due to the use of hGH, which was banned by the FDA in 1985.
Second generation growth hormone (early 1980s)
In 1981, Genentech developed a recombinant human growth hormone containing 192 amino acids, met rhGH, using E. coli inclusion body technology.
Compared with natural hGH, there is one more methionine residue at the N-terminal, also known as somatorem (protropin?).
The disadvantages of this kind of growth hormone are: the extraction and renaturation process is complex, easy to pollute, not completely consistent with natural hGH, the antibody production rate is as high as 64%, low purity and low activity, which affect the therapeutic effect, so it is eliminated.
Third generation growth hormone (mid-1980s)
The growth hormone synthesized by common E. coli gene expression technology contains 191 amino acids, but the structure of the protein is different from that of human pituitary growth hormone.
The antibody production rate is still high, the secretion and extraction process is complex, easy to pollute, and easy to bring in impurities, resulting in allergic reaction.
Fourth generation growth hormone (late 1980s)
The growth hormone containing 191 amino acids synthesized by mammalian cell recombinant DNA technology has the advantages that the product is closer to the structure of natural growth hormone, but its disadvantages are: ① high requirements for cell culture, slow reproduction speed and low yield; ② Adenovirus contamination - infection of animal origin; ③ Proliferation promoting drug contamination - tumorigenesis. Therefore, it is only used by a few manufacturers at present.
Fifth generation growth hormone (1990s)
Jin Lei synthesized growth hormone with E. coli secretory gene expression technology, and the product was directly secreted outside the cell.
Its amino acid content, sequence and protein structure are completely consistent with human pituitary growth hormone, and its biological activity, potency, purity and absorption rate are very high. While minimizing the treatment cost, it ensures the safety, effectiveness and stability of the product.
Most of the world's leading manufacturers have adopted, and the products have occupied more than 95% of the global market share.