Young Jacques, Chanson Philippe, Salenave Sylvie, Noël Michèle, Brailly Sylvie, O'Flaherty Martín, Schaison Gilbert, Rey Rodolfo
Service d'Endocrinologie et des Maladies de la Reproduction, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, 94270 Le Kremlin Bicêtre cedex, France.
J Clin Endocrinol Metab. 2005 Feb;90(2):724-8. doi: 10.1210/jc.2004-0542. Epub 2004 Nov 9.
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 sc 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 AMH 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.
血清抗苗勒管激素（AMH）是青春期前支持细胞的标志物，在青春期会下降，这是睾丸睾酮（T）产生的早期迹象。当T合成或作用受损时，出生后最初几个月及青春期时血清AMH异常升高，但在这两个时期之间则正常。我们推测在缺乏雄激素抑制的情况下，促卵泡生成素（FSH）可能是AMH上调的原因。为了验证这一假设，我们对8名年龄在18至31岁之间未经治疗的先天性低促性腺激素性性腺功能减退患者给予重组人（rh）FSH。这种情况是研究FSH对AMH产生影响的理想状态，因为它避免了内源性促性腺激素和T的干扰。患者每天皮下注射150 IU rhFSH，持续1个月，其中7名患者随后接受rhFSH加人绒毛膜促性腺激素（hCG；1500 UI，肌肉注射，每周两次）联合治疗2个月。在治疗前、rhFSH治疗期间每10天以及rhFSH和hCG联合治疗期间每月检测血浆中的促性腺激素、T、AMH和抑制素B。治疗前所有激素水平均处于青春期前水平。尽管促黄体生成素（LH）和T没有变化，但给予FSH 20天后，AMH和抑制素B水平逐渐升高。然而，与单独使用rhFSH不同，rhFSH加hCG联合刺激睾丸会显著抑制AMH的分泌，并使循环抑制素B水平适度但显著降低。我们得出结论，在睾丸处于青春期前阶段时，FSH会刺激AMH的产生。此外，rhFSH和hCG联合刺激睾丸期间血清AMH的下降与以下概念一致：在青春期发育和成年期，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。最后，hCG诱导的抑制素B下降表明，在人类中，正如先前在猴子中所证明的那样，睾丸T也能够抑制抑制素B的分泌。
