Eakman G D, Dallas J S, Ponder S W, Keenan B S
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0363, USA.
J Clin Endocrinol Metab. 1996 Mar;81(3):1217-23. doi: 10.1210/jcem.81.3.8772602.
Testosterone (T) administration to pubertal boys increases spontaneous GH secretion. It is not known whether this occurs via pituitary or hypothalamic mechanisms. We evaluated the GH secretion of 12 boys, aged 13.67 +/- 0.37 yr (mean +/- SE), diagnosed with constitutional delay in growth and adolescence. The evaluation was made both before and after 3 months of treatment with T or the nonaromatizable androgen, 5 alpha-dihydrotetosterone. Serum for determination of spontaneous GH secretion was sampled every 20 min for 24 h. Pituitary responsiveness was assessed by the administration of GHRH with sampling of GH at intervals for the next 2 h. This was also done with pyridostigmine (PDS) pretreatment to assess the effects of somatostatin. The dose of androgen used was 80 mg/m2 month. All tests were then repeated during treatment. Spontaneous GH secretion was analyzed by the Cluster method. The response to GHRH was measured as the area under the curve. Somatostatin effects were quantified as the difference in responsiveness between the two GHRH tests performed at each admission: one without prior PDS administration and one in which somatostatin was blocked by PDS. Treatment with T increased mean spontaneous GH secretion from 2.25 +/- 0.34 micrograms/L before treatment to 6.77 +/- 0.69 micrograms/L (mean +/- SE; P < 0.001) and mean spontaneous peak height from 5.62 +/- 1.05 to 17.21 +/- 1.52 micrograms/L (mean +/- SE; P < 0.001). No significant differences between pretreatment and treatment evaluations for any spontaneous GH secretory parameters were seen in 5 alpha-dihydrotestosterone-treated patients, except that maximum peak height was decreased after treatment (P < 0.02). In T treated patients, the GHRH stimulation tests without prior PDS administration changed from 84.14 +/- 34.54 total micrograms/L before to 102.3 +/- 35.82 total micrograms/L (mean +/- SE; P = NS) after androgen treatment. PDS pretreatment produced an increase in responsiveness to GHRH over the test without PDS pretreatment. This increase was 127.03 +/- 35.68 total micrograms/L before T treatment; after T treatment, this increase was 78.38 +/- 57.6 total micrograms/L (mean +/- SE; P = NS). T treatment, via an estrogen-dependent mechanism, caused increased GH pulse amplitude, thereby increasing the mean serum GH concentration. This increase was not the result of increased pituitary responsiveness or decreased somatostatin tone. This indicates that T exerted its effect on GH via increased GHRH pulse amplitude.
对青春期男孩给予睾酮（T）可增加生长激素（GH）的自发性分泌。目前尚不清楚这是通过垂体机制还是下丘脑机制发生的。我们评估了12名年龄为13.67±0.37岁（均值±标准误）、被诊断为体质性生长和青春期延迟的男孩的GH分泌情况。在给予T或不可芳香化雄激素5α-双氢睾酮治疗3个月之前和之后均进行了评估。每20分钟采集一次血清以测定24小时的自发性GH分泌。通过给予生长激素释放激素（GHRH）并在接下来的2小时内间隔采集GH来评估垂体反应性。对使用吡啶斯的明（PDS）进行预处理以评估生长抑素的作用时也进行了同样的操作。使用的雄激素剂量为80mg/m²·月。然后在治疗期间重复所有测试。通过聚类法分析自发性GH分泌情况。将对GHRH的反应测量为曲线下面积。生长抑素的作用通过每次入院时进行的两次GHRH测试之间的反应性差异来量化：一次未预先给予PDS，一次生长抑素被PDS阻断。用T治疗可使平均自发性GH分泌从治疗前的2.25±0.34μg/L增加至6.77±0.69μg/L（均值±标准误；P<0.001），平均自发性峰值高度从5.62±1.05μg/L增加至17.21±1.52μg/L（均值±标准误；P<0.001）。在接受5α-双氢睾酮治疗的患者中，除了治疗后最大峰值高度降低（P<0.02）外，任何自发性GH分泌参数在预处理和治疗评估之间均未观察到显著差异。在接受T治疗的患者中，未预先给予PDS的GHRH刺激试验从治疗前的总84.14±34.54μg/L变为雄激素治疗后的102.3±35.82μg/L（均值±标准误；P=无显著性差异）。与未进行PDS预处理的测试相比，PDS预处理使对GHRH的反应性增加。这种增加在T治疗前为127.03±35.68μg/L；T治疗后，这种增加为78.38±57.6μg/L（均值±标准误；P=无显著性差异）。T治疗通过雌激素依赖性机制导致GH脉冲幅度增加，从而增加平均血清GH浓度。这种增加不是垂体反应性增加或生长抑素张力降低的结果。这表明T通过增加GHRH脉冲幅度对GH发挥作用。
