GH has a potentially wide range of therapeutic uses (Table 11.6). To date, however, its major application has been for the treatment of short stature. hGH extracted from human pituitary glands was first used to treat pituitary dwarfism (i.e. caused by suboptimal pituitary GH secretion) in 1958. It has subsequently proven effective in the treatment of short stature caused by a variety of other conditions, including:
• idiopathic short stature;
• chronic renal failure.
The use of hGH extracted from the pituitaries of deceased human donors came to an abrupt end in 1985, when a link between treatment and Creutzfeld-Jacob disease (CJD, a rare, but fatal,
Table 11.6 Some actual or likely therapeutic uses for hGH. Refer to text for details
Treatment of short stature caused by GH deficiency
Treatment of defective growth caused by various diseases/medical conditions
Induction of lactation
Treatment of obesity
Induction of ovulation neurological disorder) was discovered. In this year, a young man, who had received hGH therapy some 15 years previously, died from CJD, which, investigators concluded, he had contracted from infected pituitary extract (CJD appears to be caused by a prion). At least an additional 12 CJD cases suspected of being caused in the same way have subsequently been documented. Fortunately, several recombinant hGH (rhGH) preparations were coming on-stream at that time (Table 11.7), and now all hGH preparations used clinically are derived from recombinant sources. Currently, in excess of 20 000 people are in receipt of rhGH therapy.
rhGH was first produced in E. coli in the early 1980s. The initial recombinant preparations differed from the native human hormone only in that they contained an extra methionine residue (due to the AUG start codon inserted at the beginning of the gene). Subsequently, a different cloning strategy allowed production in E. coli of products devoid of this terminal methionine.
In vitro analysis, including tryptic peptide mapping, amino acid analysis and comparative im-munoassays, shows the native and recombinant forms of the molecule to be identical. Clinical trials in humans have also confirmed that the recombinant version promotes identical biological responses to the native hormone. rhGH was first purified (on a laboratory scale) by Genentech scientists using the strategy outlined in Figure 11.9. A somewhat similar strategy is likely used in its process-scale purification.
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