Keenan B S, Richards G E, Mercado M, Dallas J S, Eakman G D, Baumann G
Department of Pediatrics, The University of Texas Medical Branch, Galveston 77555-0363, USA.
Metabolism. 1996 Dec;45(12):1521-6. doi: 10.1016/s0026-0495(96)90182-1.
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 5alpha-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 microg/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 microg/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.
男性青春期与血浆生长激素（GH）和胰岛素样生长因子-I（IGF-I）浓度升高以及线性生长加速有关。这些作用可通过给予睾酮（T）来重现。为了进一步阐明青春期生长的潜在机制，我们对14名青春期延迟且身材矮小的男孩进行治疗，其中7名给予T，7名给予5α-双氢睾酮（DHT），并比较其对血浆GH、IGF-I和GH结合蛋白（GHBP）浓度的影响。在给予庚酸睾酮或庚酸DHT三或四剂之前和之后，测量平均12小时GH浓度（上午8点至晚上8点）以及血浆IGF-I、T、DHT和GHBP水平，并在此期间测量身高增长速度（HV）。T治疗导致平均GH从3.3微克/升增加至12.0微克/升（P <.005），IGF-I从22.3纳摩尔/升增加至45.4纳摩尔/升（P <.01）。治疗期间，HV为11.0±1.1厘米/年，与正常青春期生长一致，血浆T为22.5±5.3纳摩尔/升。该组中GHBP从937皮摩尔/升降至521皮摩尔/升（P <.025）。DHT治疗导致平均GH从4.3微克/升小幅降至2.9微克/升（P <.025），IGF-I从29.4纳摩尔/升降至27.2纳摩尔/升（无统计学意义[NS]）。治疗期间，HV为9.3±1.1，与T治疗获得的HV无显著差异，注射后1周血浆DHT为24.2纳摩尔/升，2周时为29.2纳摩尔/升。同样，GHBP从928皮摩尔/升降至698皮摩尔/升（P <.025）。T治疗导致的GHBP下降显然是由于雄激素受体依赖性机制，因为在使用不可芳香化雄激素DHT治疗期间也观察到了相同的效果。这种作用与从婴儿期到青春期中期GHBP正常的随时间上升趋势相反。决定上升趋势的因素尚不清楚，但显然与性激素和GH的血浆浓度无关。尽管GHBP（可能还有GH受体）水平适度下降，但T治疗后IGF-I仍增加，这很可能是由于GH大幅增加，可能超过了GHBP/GH受体的适度下降。
