Exogenous 20K growth hormone (GH) suppresses endogenous 22K GH secretion in normal men

The physiological and pharmacological functions of the 20-kDa human GH (20K -hGH) isoform are unknown. We conducted a pharmacokinetic study of recombin ant 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 2 100 h. Serum 20K- and 22K-hGH let els were monitored every 30 min for 24 h by specific enzyme-linked immunosorbent assays. Serum free fatty acid, insu lin-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 leve ls 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 h alf-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. Se rum insulin and glucose levels did not change significantly within 24 h. Th ese results suggested that: 1) regulation of 20K-hGH secretion is physiolog ically the same as that of 22K-hGH; 2) the pharmacokinetics after sc inject ion of 20K-hGH are comparable with those of 22K-hGH; 3) 20K-hGH regulates h GH secretion through "GH-induced negative feedback mechanisms"; and 4) admi nistration of 20K-hGH is expected to exert GH actions (growth-promoting act ivity and lipolytic activity). Monitoring of serum 20K- and 22K-hGH levels may be useful in evaluating the effects of administered GH isoforms on thei r own release fi om the pituitary.