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Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men

Institute of Biological Science (Y.H., M.H., K.M.), Mitsui Pharmaceuticals, Inc., Chiba 297-0017; Clinical Development Department (T.K., A.M., Y.S.), Mitsui Pharmaceuticals, Inc., Tokyo 103-0027; Komagome-higashi Clinic (M.T.), Kiyaku-kai Medical Corporation Hohsen Clinic, Tokyo 170-0003; and Department of Endocrinology and Metabolism (T.T.), National Children’s Medical Research Center, Tokyo 154-8509, Japan

Address correspondence and requests for reprints to: Yoshihide Hashimoto, Ph.D., Senior Scientist, Institute of Biological Science, Mitsui Pharmaceuticals, Inc., 1900–1 Togo, Mobara, Chiba 297-0017, Japan.

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.

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