Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males

GH is being used by elite athletes to enhance sporting performance. To exam ine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) admini stration could be detected through suppression of non-22-kDa isoforms of GH , we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) ran domized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmac ia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoa ssays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofun ctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kD a and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups . In identical exercise studies repeated between 24 and 96 h after cessatio n of treatment, the magnitude of the responses of all GH isoforms was suppr essed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adu lt males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the dearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kD a or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.