Dr. Alfred Jost pioneered the field of reproductive endocrinology with his seminal observation that two hormones produced by the testes are required for the male embryo to develop a normal internal reproductive tract. T induces the Wolffian ducts to differentiate into epididymides, vasa deferens, and seminal vesicles. Müllerian inhibiting substance (MIS) causes regression of the Müllerian ducts, which in its absence would normally develop into the Fallopian tubes, uterus, and upper vagina as is observed in female embryos. This review will summarize our current understanding of molecular mechanisms underlying the function of MIS both as a fetal gonadal hormone that causes Müllerian duct regression and as an adult hormone, the roles for which are currently being investigated, i.e., inhibition of steroidogenesis, germ cell development, and cancer. We will also address the regulation of MIS expression as one of the first genes expressed after the commitment of the bipotential gonads to differentiate into testes under the influence of SRY, the gene on the sex-determining region of the Y chromosome. We will discuss what is known regarding MIS signal transduction, which as with other members of the TGFbeta family of growth and differentiation factors, occurs through a heteromeric complex of single transmembrane serine/threonine kinase receptors to effect downstream signaling events, including Smad, nuclear factor-kappaB, beta-catenin, and p16 activation. Finally, we will assess the clinical relevance of studying MIS in patients with persistent Müllerian duct syndrome and our efforts to determine the therapeutic value of MIS for patients with ovarian and other MIS receptor-expressing cancers.

中文翻译：

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苗勒抑制物质：具有指导意义的发育激素，具有诊断和可能的治疗用途。

阿尔弗雷德·乔斯特（Alfred Jost）博士开创了生殖内分泌学领域，他的开创性观察表明，雄性胚胎发育正常的内部生殖道需要睾丸产生两种激素。T诱导Wolffian导管分化为附睾，输精管和精囊。苗勒氏抑制物质（MIS）导致苗勒氏管退化，如缺少，通常会发展成输卵管，子宫和上阴道，如在女性胚胎中观察到的那样。这篇综述将总结我们目前对MIS作为潜在的胎儿性腺激素（导致缪勒管退化）和成年激素功能的分子机制的理解，目前正在研究其作用，即抑制类固醇生成，生殖细胞发育和癌症。我们还将解决MIS表达的调控问题，该基因是双电位性腺致力于在SRY的影响下分化成睾丸后表达的第一个基因，该基因位于Y染色体的性别决定区域。我们将讨论有关MIS信号转导的已知信息，与TGFbeta系列生长和分化因子家族的其他成员一样，它是通过单个跨膜丝氨酸/苏氨酸激酶受体的异源复合物发生的，从而影响下游信号转导事件，包括Smad，核因子-kappaB，β-catenin和p16激活。最后，我们将评估在患有持续性Müllerian管综合征的患者中研究MIS的临床相关性，以及我们努力确定MIS对卵巢癌和其他表达MIS受体的癌症患者的治疗价值。