Androgen regulation of growth hormone binding protein

Abstract

Male puberty is associated with elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I), as well as accelerated linear growth. These effects can be reproduced by administration of testosterone (T). To further elucidate the mechanisms underlying pubertal growth, we treated 14 boys with delayed puberty and short stature with either T (n = 7) or 5α-dihydrotestosterone (DHT) (n = 7) and compared the effect on plasma concentrations of GH, IGF-I, and GH binding protein (GHBP). Before treatment and after either three or four doses of T enanthate or DHT heptanoate, mean 12-hour GH concentration (8 am to 8 pm) and plasma IGF-I, T, DHT, and GHBP levels were measured, and height velocity (HV) was measured over this interval. T treatment resulted in an increase of mean GH from 3.3 to 12.0 μg/L ( P < .005) and of IGF-I from 22.3 to 45.4 nmol/L ( P < .01). During treatment, HV was 11.0 ± 1.1 cm/yr, consistent with normal pubertal growth, 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 GH from 4.3 to 2.9 μg/L ( P < .025) and of IGF-I from 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 treatment, 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 apparently due to an androgen receptor-dependent mechanism, since the same effect was seen during treatment with the nonaromatizable androgen, DHT. This effect is opposite to the normal chronological trend upward for GHBP, which occurs from infancy into midpuberty. Factors determining the upward trend are not known, but are evidently independent of the plasma concentration of sex hormones and GH. The increase in IGF-I in response to T treatment despite a moderate decline in GHBP (and possibly GH receptor) levels is most likely due to the large increase in GH, which may override a modest decrease in GHBP/GH receptor.