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Background: Two molecular forms of human GH (hGH) have been shown to be biologically active. The 20 kDa form has been reported to have weaker diabetogenic and lipolytic actions than the 22 kDa form. Objective: To analyze the carbohydrate metabolism of 20 kDa and 22 kDa hGH, using the adult male spontaneous dwarf rat (SDR), which is GH deficient. Design: SDRs were given 20 kDa or 22 kDa hGH in doses of 125 mg/rat or 500 mg/rat, or saline, for 10 days, and their weight, serum IGF-I, glucose, insulin, leptin and body composition were measured. Results: Weight and serum IGF-I increased both in the 20 kDa and 22 kDa groups, but IGF-I concentrations were significantly lower in the 20 kDa group than in the 22 kDa group. Serum glucose was not increased by either 20 kDa or 22 kDa hGH, whereas insulin was significantly increased after the higher dose of the 22 kDa hGH. Although blood concentrations of leptin were decreased by both 20 kDa and 22 kDa hGH, values were lower in the high-dose 20 kDa group than in the group given the same dose of 22 kDa hGH. Both forms of GH increased the percentage body water and body protein content, and decreased the percentage of body fat by the same degree. The observation that the higher dose of the 22 kDa hGH increased insulin concentrations without changing blood glucose demonstrates that this concentration of the hormone induces insulin resistance, whereas the same dose of 20 kDa hGH does not. Conclusions:The results can be interpreted to indicate that the higher dose of the 22 kDa hGH has diabetogenic activity, as reported previously, whereas the 20 kDa hGH has lower diabetogenic activity. The 20 kDa form of hGH may therefore be more useful in treating adult GH deficiency, especially those with severe obesity.

The physiological and pharmacological functions of the 20-kDa human GH (20K-hGH) isoform are unknown. We conducted a pharmacokinetic study of recombinant 20K-hGH in human subjects (Phase I clinical trial). Placebo or 20K-hGH was administered sc to normal men (20-31 yr of age, n = 6-8 per group) at 2100 h. Serum 20K- and 22K-hGH levels were monitored every 30 min for 24 h by specific enzyme-linked immunosorbent assays. Serum free fatty acid, insulin-like growth factor I, insulin, and glucose levels were measured for 24 h. In the placebo group, the secretion profiles of endogenous 20K- and 22K-hGH were pulsatile and similar to each other. The proportion of 20K- to 22K-hGH was fairly constant. In the 20K-hGH-treated groups, serum 20K-hGH levels increased in a dose-dependent manner over the dose range of 0.01-0.1 mg/kg. Maximum serum 20K-hGH levels were reached at 3-4 h and decreased with half-lives of 2-3 h. Marked suppression of endogenous 22K-hGH secretion was observed in a time-dependent manner. Serum free fatty acid and insulin-like growth factor I levels were significantly elevated (P < 0.01) at 4, 8, and 12 h and at 8, 12, and 24 h after 20K-hGH administration, respectively. Serum insulin and glucose levels did not change significantly within 24 h. These results suggested that: 1) regulation of 20K-hGH secretion is physiologically the same as that of 22K-hGH; 2) the pharmacokinetics after sc injection of 20K-hGH are comparable with those of 22K-hGH; 3) 20K-hGH regulates hGH secretion through "GH-induced negative feedback mechanisms"; and 4) administration of 20K-hGH is expected to exert GH actions (growth-promoting activity and lipolytic activity). Monitoring of serum 20K- and 22K-hGH levels may be useful in evaluating the effects of administered GH isoforms on their own release from the pituitary.

This result suggests that the increased cost of the conditioning regimen offsets the reduced cost of hospitalization in RIST. Although some differences were observed in the details of the cost, the total cost and mean survival were comparable between CST and RIST, and this result was confirmed by a probabilistic sensitivity analysis.