Müllerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications.
Müllerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications.
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DOI：
10.1210/edrv.22.5.0445
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发表时间：
2001-10
影响因子：
20.3
通讯作者：
J. Teixeira;S. Maheswaran;P. Donahoe
中科院分区：
文献类型：
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作者：
J. Teixeira;S. Maheswaran;P. Donahoe
阿尔弗雷德·约斯特博士开创了生殖内分泌学领域，他的开创性观察表明，男性胚胎发育正常的内部生殖道需要睾丸产生的两种激素。T诱导沃尔夫管分化为附睾、输精管和精囊。苗勒管抑制物质（MIS）导致苗勒管退化，在其缺失的情况下，苗勒管通常会发育成输卵管，子宫和阴道上部，如在雌性胚胎中观察到的那样。这篇综述将总结我们目前对MIS作为导致苗勒管退化的胎儿性腺激素和作为成人激素的功能的分子机制的理解，其作用目前正在研究中，即，抑制类固醇生成、生殖细胞发育和癌症。我们还将解决MIS表达的调节，作为双能性腺在SRY（Y染色体性别决定区的基因）的影响下分化为睾丸后表达的第一个基因之一。我们将讨论什么是已知的MIS信号转导，这与其他成员的TGF β家族的生长和分化因子，发生通过一个异聚复合物的单一跨膜丝氨酸/苏氨酸激酶受体影响下游信号事件，包括Smad，核因子-κ B，β-连环蛋白，和p16激活。最后，我们将评估MIS在持续性苗勒管综合征患者中的临床相关性，以及我们为确定MIS对卵巢癌和其他MIS受体表达癌患者的治疗价值所做的努力。
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.