Testicular anti-Mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism
Testicular anti-Mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism
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DOI：
10.1210/jc.2004-0542
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Rey, R
中科院分区：
文献类型：
--
作者：
Young, J;Chanson, P;Rey, R
血清抗苗勒管激素 (AMH) 是一种青春期前支持细胞标记物，在青春期期间会下降，这是睾丸睾酮 (T) 产生的早期迹象。当 T 合成或作用受损时，血清 AMH 在出生后最初几个月和青春期异常高，但在这两个时期之间正常。我们推测，在没有雄激素抑制的情况下，FSH 可能是 AMH 上调的原因。为了检验这一假设，我们对 8 名年龄在 18-31 岁、患有未经治疗的先天性低促性腺激素性性腺功能减退症的患者施用重组人 (rh) FSH。这种情况非常适合研究 FSH 对 AMH 产生的影响，因为它避免了内源性促性腺激素和 T 的干扰。患者每天接受 150 IU rhFSH 注射，持续 1 个月，随后其中 7 名患者接受 rhFSH 加人绒毛膜促性腺激素（hCG；1500 UI 肌注，每周两次）联合治疗，持续 2 个月。治疗前，rhFSH 治疗期间每 10 天测量一次血浆中的促性腺激素、T、AMH 和抑制素 B，rhFSH 和 hCG 联合治疗期间每月测量一次。治疗前所有激素均处于青春期前水平。尽管 LH 和 T 没有变化，但 AMH 和抑制素 B 水平在 FSH 给药 20 天后逐渐升高。然而，与单独使用 rhFSH 相比，rhFSH 与 hCG 联合刺激睾丸可显着抑制 AAM 的分泌，并诱导循环抑制素 B 水平适度但显着降低。我们得出结论，当睾丸处于青春期前阶段时，FSH 会刺激睾丸中 AMH 的产生。此外，rhFSH和hCG联合刺激睾丸期间血清AMH的降低与青春期发育和成年期间LH驱动的睾丸雄激素的抑制作用超过FSH对支持细胞产生AMH的刺激作用的概念一致。最后，hCG 诱导的抑制素 B 减少表明，正如之前在猴子中所证明的那样，在人类中，睾丸 T 也能够抑制抑制素 B 的分泌。
Serum anti-Mullerian hormone (AMH), a prepubertal Sertoli cell marker, declines during puberty as an early sign of testicular testosterone (T) production. When T synthesis or action is impaired, serum AMH is abnormally high in the first months after birth and at puberty but normal between these two periods. We postulated that FSH might be responsible for AMH up-regulation in the absence of androgen inhibition.To test this hypothesis, we administered recombinant human (rh) FSH to eight patients aged from 18-31 yr with untreated congenital hypogonadotropic hypogonadism. This situation is ideal to study the effect of FSH on AMH production because it avoids interference by endogenous gonadotropins and T. The patients received daily se injections of 150 IU rhFSH for 1 month, followed in seven of them by a combined treatment of rhFSH plus human chorionic gonadotropin (hCG; 1500 UI im, twice a week) for 2 months. Gonadotropins, T, AMH, and inhibin B were measured in plasma before treatment every 10 d during rhFSH treatment and every month during combined rhFSH and hCG treatments.All hormones were at prepubertal levels before treatment. Although LH and T did not vary, AMH and inhibin B levels gradually increased after 20 d of FSH administration. However, in contrast to rhFSH alone, the combined rhFSH plus hCG stimulation of the testis dramatically suppresses the secretion of AAM and induced a modest but significant reduction of circulating inhibin B levels.We conclude that FSH stimulates AMH production in the testis when it is at a prepubertal stage. In addition, the decrease of serum AMH during combined rhFSH and hCG testicular stimulation is in agreement with the concept that during pubertal development and in adult life, the suppressive effect of LH-driven testicular androgens outweighs the stimulating effect of FSH on AMH production by Sertoli cells. Finally, the hCG-induced decrease in inhibin B suggests that in humans, as previously demonstrated in monkeys, testicular T is also able to inhibit inhibin B secretion.