Rey R, Lordereau-Richard I, Carel J C, Barbet P, Cate R L, Roger M, Chaussain J L, Josso N
Unité de Recherches sur l'Endocrinologie du Développement (INSERM), Ecole Normale Supérieure, Montrouge, France.
J Clin Endocrinol Metab. 1993 Nov;77(5):1220-6. doi: 10.1210/jcem.77.5.8077315.
Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance or factor, is produced by Sertoli cells from fetal life until puberty. In the present study, AMH, testosterone (T), LH, and FSH were measured by immunochemical methods in the serum of 50 boys with normal or delayed pubertal development, 4 patients with suspected androgen insensitivity, and 11 patients with either central (CPP) or gonadotropin-independent (GIPP) precocious puberty to investigate the hormonal regulatory mechanisms of AMH secretion at puberty. An inverse relationship between AMH and T levels was demonstrated. In boys with normal or delayed puberty with T concentrations below 6.7 nmol/L, AMH values were elevated (mean +/- SEM, 22.4 +/- 3.1 micrograms/L) and widely dispersed. In subjects with T levels over 6.7 nmol/L, AMH levels were uniformly low (3.4 +/- 0.5 micrograms/L), except in patients with suspected androgen insensitivity. No significant relationship was found between AMH and gonadotropin levels. Similar results were obtained in patients with either CPP or GIPP. Longitudinal studies were performed on four boys with CPP and two with GIPP before and after treatment. At the time of diagnosis, the T concentration was high, and AMH levels were usually low in CPP and GIPP patients alike. When appropriate treatment was initiated, the T concentration was normalized within 2-4 weeks, but restoration of prepubertal AMH levels required several months. Mature Sertoli cells were observed in testicular biopsies performed in three patients with untreated GIPP. Our results suggest that gonadotropins are not directly implicated in repression of AMH synthesis at puberty, but, rather, that the decrease in AMH production is the consequence of an androgen-mediated, long term, reversible chain of events leading to morphological and functional maturation of the Sertoli cells. Thus, the fall in serum AMH levels appears to be an excellent marker of Sertoli cell pubertal development.
抗苗勒管激素（AMH），也称为苗勒管抑制物质或因子，从胎儿期到青春期由支持细胞产生。在本研究中，采用免疫化学方法测定了50例青春期发育正常或延迟的男孩、4例疑似雄激素不敏感患者以及11例中枢性（CPP）或促性腺激素非依赖性（GIPP）性早熟患者血清中的AMH、睾酮（T）、促黄体生成素（LH）和促卵泡生成素（FSH），以研究青春期AMH分泌的激素调节机制。结果显示AMH与T水平呈负相关。在青春期正常或延迟且T浓度低于6.7 nmol/L的男孩中，AMH值升高（平均值±标准误，22.4±3.1μg/L）且分布广泛。在T水平超过6.7 nmol/L的受试者中，AMH水平均较低（3.4±0.5μg/L），疑似雄激素不敏感患者除外。未发现AMH与促性腺激素水平之间存在显著关系。CPP或GIPP患者也得到了类似结果。对4例CPP男孩和2例GIPP男孩在治疗前后进行了纵向研究。诊断时，CPP和GIPP患者的T浓度均较高，而AMH水平通常较低。开始适当治疗后（2 - 4周内），T浓度恢复正常，但青春期前AMH水平的恢复需要数月时间。在3例未经治疗的GIPP患者的睾丸活检中观察到了成熟的支持细胞。我们的结果表明，促性腺激素在青春期并非直接参与抑制AMH合成，相反，AMH产生的减少是雄激素介导的、长期的、可逆的一系列事件的结果，这些事件导致支持细胞的形态和功能成熟。因此，血清AMH水平的下降似乎是支持细胞青春期发育的一个良好标志。
