ANDROGEN REGULATION OF GROWTH-HORMONE BINDING-PROTEIN

Male puberty is associated with elevated plasma concentrations of grow th hormone (GH) and insulin-like growth factor-I (IGF-I), as well as a ccelerated linear growth. These effects can be reproduced by administr ation of testosterone (T). To further elucidate the mechanisms underly ing pubertal growth, we treated 14 boys with delayed puberty and short stature with either T (n = 7) or 5 alpha-dihydrotestosterone (DHT) (n = 7) and compared the effect on plasma concentrations of GH, IGF-I, a nd GH binding protein (GHBP). Before treatment and after either three or four doses of T enanthate or DHT heptanoate, mean 12-hour OH concen tration (8 AM to 8 PM) and plasma IGF-I, T, DHT, and GHBP levels were measured, and height velocity (HVJ was measured over this interval. T treatment resulted in an increase of mean GH from 3.3 to 12.0 mu g/L ( P < .005) and of IGF-I from 22.3 to 45.4 nmol/L (P < .01). During trea tment, HV was 11.0 +/- 1.1 cm/yr, consistent with normal pubertal grow th, and plasma T was 22.5 +/- 5.3 nmol/L. GHBP decreased in this group from 937 to 521 pmol/L (P < .025). DHT treatment resulted in a small decrease of mean OH from 4.3 to 2.9 mu g/L (P < .025) and of IGF-I fro m 29.4 to 27.2 nmol/L (nonsignificant [NS]. During treatment, HV was 9 .3 +/- 1.1;, not significantly different from the HV obtained with T t reatment, and plasma DHT was 24.2 nmol/L at 1 week and 29.2 at 2 weeks postinjection. Likewise, there was a decrease in GHBP from 928 to 698 pmol/L (P < .025). The decline in GHBP with T treatment was apparentl y due to an androgen receptor-dependent mechanism, since the same effe ct was seen during treatment with the nonaromatizable androgen, DHT. T his effect is opposite to the normal chronological trend upward for GH BP, which occurs from infancy into midpuberty. Factors determining the upward trend are not known, but are evidently independent of the plas ma concentration of sex hormones and GH. The increase in IGF-I in resp onse to T treatment despite a moderate decline in GHBP (and possibly G H receptor) levers is most likely due to the large increase in OH, whi ch may override a modest decrease in GHBP/GH receptor. Copyright (C) 1 996 by W.B. Saunders Company