Exogenous 20K growth hormone (GH) suppresses endogenous 22K GH secretion in normal men
| Autor: | Akira Mizuchi, Toshiaki Tanaka, Michio Tsunoo, Kazunori Mabuchi, Takeshi Kamioka, Masaharu Hosaka, Yukio Shimazaki, Yoshihide Hashimoto |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Injections Subcutaneous Clinical Biochemistry Phases of clinical research Endogeny Enzyme-Linked Immunosorbent Assay Biology Fatty Acids Nonesterified Placebo Biochemistry Endocrinology Pharmacokinetics Reference Values Internal medicine medicine Humans Secretion Insulin-Like Growth Factor I Human Growth Hormone Insulin Growth factor Biochemistry (medical) Growth hormone secretion Peptide Fragments Recombinant Proteins embryonic structures hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 85(2) |
| ISSN: | 0021-972X |
| Popis: | 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 (P0.01) 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. |
| Databáze: | OpenAIRE |
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