Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan.
Mol Cell Endocrinol. 2011 Feb 20;333(2):190-9. doi: 10.1016/j.mce.2010.12.025. Epub 2010 Dec 25.
Anti-Müllerian hormone (AMH) plays an important role in male sex differentiation in vertebrates. AMH produced by Sertoli cells of the fetal testis induces regression of the Müllerian duct in mammalian species. In alligators, sexual differentiation is controlled by the temperature during egg incubation, termed temperature-dependent sex determination (TSD). The TSD mechanism inducing sex differentiation is thought to be unique and different from that of genetic sex determination as no gene such as the SRY of mammals has been identified. However, many of the genes associated with gonadal differentiation in mammals also are expressed in the developing gonads of species exhibiting TSD. To clarify the molecular mechanisms associated with gonad formation during the temperature-sensitive period (TSP), we have cloned the full length AMH gene in the alligator, and quantitatively compared mRNA expression patterns in the gonad-adrenal-mesonephros (GAM) complex isolated from alligator embryos incubated at male and female producing temperatures. The deduced amino acid sequence of the alligator AMH cDNA showed high identity (59-53%) to avian AMH genes. AMH mRNA expression was high in the GAM of male alligator embryos at stage 24 (immediately after sex determination) and hatchlings, but suppressed in the GAM of estrogen-exposed hatchlings incubated at the male-producing temperature. In the alligator AMH proximal promoter, a number of transcriptional factors (for SF-1. GATA, WT-1 and SOX9) binding elements were also identified and they exhibit a conserved pattern seen in other species. SOX9 up-regulates transcriptional activity through the amAMH promoter region. These results suggested that AMH and SOX9 play important roles in TSD of the American alligator.
抗缪勒管激素（AMH）在脊椎动物的雄性性别分化中起着重要作用。胎儿睾丸的支持细胞产生的 AMH 诱导哺乳动物的缪勒管退化。在短吻鳄中，性别分化受卵孵化期间的温度控制，称为温度依赖性性别决定（TSD）。诱导性别分化的 TSD 机制被认为是独特的，与遗传性别决定不同，因为没有像哺乳动物的 SRY 这样的基因被识别。然而，与哺乳动物性腺分化相关的许多基因也在表现 TSD 的物种的发育性腺中表达。为了阐明在温度敏感期（TSP）期间与性腺形成相关的分子机制，我们克隆了短吻鳄全长 AMH 基因，并定量比较了在从孵化在产生雄性和雌性温度的短吻鳄胚胎中分离的性腺-肾上腺-中肾（GAM）复合体中 mRNA 表达模式。短吻鳄 AMH cDNA 的推导氨基酸序列与禽类 AMH 基因具有高度同源性（59-53%）。AMH mRNA 表达在 24 期（性别决定后立即）和孵化幼鳄的 GAM 中较高，但在孵化幼鳄的 GAM 中被抑制，这些幼鳄在产生雄性的温度下暴露于雌激素。在短吻鳄 AMH 近端启动子中，还鉴定出许多转录因子（SF-1、GATA、WT-1 和 SOX9）结合元件，它们表现出与其他物种相同的保守模式。SOX9 通过 amAMH 启动子区域上调转录活性。这些结果表明，AMH 和 SOX9 在美洲短吻鳄的 TSD 中发挥重要作用。
