Activation of the somatotropic axis by testosterone in adult men: Evidence for a role of hypothalamic growth hormone-releasing hormone
Activation of the somatotropic axis by testosterone in adult men: Evidence for a role of hypothalamic growth hormone-releasing hormone
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DOI：
10.1159/000071310
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发表时间：
2003-06-01
影响因子：
4.1
通讯作者：
degli Uberti, E
中科院分区：
文献类型：
--
作者：
Bondanelli, M;Ambrosio, MR;degli Uberti, E
已知睾酮 (T) 会影响生长激素 (GH) 轴。然而，T 激活 GH 分泌的机制仍有待阐明。动物和人类的现有数据表明，停止注射生长抑素 (SRIH) 会诱导 GH 释放激素 (GHRH) 介导的 GH 反弹释放，并且越来越多的证据表明，停止注射 SRIH 可能是探测体内 GHRH 功能的有用测试。为了研究雄激素对人类 GH 释放的刺激作用是否可以通过下丘脑 GHRH 张力的激活来解释，我们评估了 10 名年龄为 29.6 +/- 2.4 岁（平均值 +/- SEM）的患者对 SRIH 戒断的血浆 GH 反应，这些患者被诊断为高促性腺激素性性腺功能减退症，在使用 T 庚酸（每 3 周 250 mg，每 3 周 250 mg， i.m.），以及 10 名健康男性，年龄 26.7 +/- 2.8 岁。为了验证 T 对 GH 分泌的调节是否也可以通过 SRIH 音调和/或垂体可释放池的变化来介导，我们检查了同一个体对 GHRH 和 L-精氨酸 (ARG) 组合的 GH 分泌反应。未经治疗的性腺功能减退患者的 GH 基础血浆浓度 (0.48 +/- 0.11 mug/l) 和 IGF-I (23.79 +/- 1.83 nmol/l) 显着低于健康男性，并且在 T 替代治疗后显着升高 (GH 1.13 +/- 0.28 mug/l; IGF-I 28.71 +/- 1.46 nmol/l)。在未经治疗的性腺功能减退男性中记录的 SRIH 停药后平均 DeltaGH 峰值 (2.65 +/- 0.86 微克/升) 显着 (p < 0.05) 低于在健康男性中观察到的峰值 (6.53 +/- 1.33 微克/升)，并且在 T 替代治疗后显着增加 (5.52 +/- 1.25 微克/升)。健康男性和未经治疗的性腺功能减退患者对 GHRH 联合 ARG（功能性 SRIH 拮抗剂）的 GH 反应没有显着差异，并且不受 T 治疗的显着影响。在健康男性和接受 T 治疗的性腺功能减退患者中，血浆 T 和雌二醇 (E-2) 水平与 SRIH 停药后的 DeltaGH 峰值显着相关，而在未经治疗的患者中则不然。在健康男性或性腺功能减退患者（T 替代之前和之后）中，GHRH + ARG 测试后的 GH 曲线下面积与 T 和 E-2 血浆水平之间没有发现显着相关性。这些发现与以下观点一致：在人类中，T 对 GH 轴的刺激作用似乎主要通过促进 GHRH 功能在下丘脑水平介导。版权所有 (C) 2003 S. Karger AG，巴塞尔。
Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 +/- 2.4 years (mean +/- SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 +/- 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 +/- 0.11 mug/l) and IGF-I (23.79 +/- 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 +/- 0.28 mug/l; IGF-I 28.71 +/- 1.46 nmol/l). The mean DeltaGH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 +/- 0.86 mug/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 +/- 1.33 mug/l) and significantly increased after T replacement therapy (5.52 +/- 1.25 mug/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E-2) levels significantly correlated with DeltaGH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E-2 plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function. Copyright (C) 2003 S. Karger AG, Basel.