Function of Ad4BP in the process of gonadal sex differentiation

抗Ad4BP免疫组织化学分析显示，性腺和肾上腺皮质是产生类固醇激素的主要组织，来自相同的细胞群。Ad4BP免疫阳性细胞分为两个群体，随后形成性腺和肾上腺皮质的原基。在这个过程中，一个有趣的问题是，为什么性别分化发生在性腺而不是肾上腺皮质的发育中。在这项研究中，我们研究了性腺分化的机制，并对转录因子Ad4BP和DAX-1的表达和功能进行了广泛的检测。这些转录因子在性腺和肾上腺皮质中表达。然而，表达谱并不相同，即Ad4BP阳性细胞并不总是DAX-1阳性。这两种转录因子在11.5DPC小鼠胚胎的生殖器脊中有明显的差异表达。在DAX-1的功能方面，DAX-1抑制了Ad4BP激活的类固醇合成基因P450的转录，DAX-1的转录受Ad4BP的控制，推测DAX-1对性腺和肾上腺特异表达基因的转录具有抑制作用。结果表明，DAX-1基因受Ad4BP调控，但其分布与Ad4BP的分布不同，提示DAX-1基因的转录可能需要除Ad4BP以外的未知转录因子。关于P450基因的转录调控，应考虑DAX-1的负调控才能理解它们的整体调控。

Immunohistochemical analyzes with anti-Ad4BP revealed that the gonads and adrenal cortex, major steroid hormone producing tissues, are originated from an identical cell population. The Ad4BP immunopositive cells divide into two populations which thereafter give rise to primordia for the gonads and adrenal cortex. In the process, one of the interesting issues is why sex differentiation occur in the gonadal but not in the adrenocortical development. In the study we examined the mechanism of gonadal sex differentiation.The expression and function of transcription factors, Ad4BP and DAX-1, were examined extensively. These transcription factors are expressed in the gonads and adrenal cortex. However, the expression profiles are not identical, ie the positive cells for Ad4BP are not always positive for DAX-1. Such distinct expression between the two transcription factors was seen in the genital ridge of 11.5 dpc mouse fetuses. With respect to the function of DAX-1, DAX-1 was shown to repress the transcription of the steroidogenic P450 genes activated by Ad4BP.The Dax-1 ge transcription was revealed to be under the control of Ad4BP.It is supposed that DAX-1 functions as the supressor against the transcription of the genes showing gonadal and adrenal specific expression. Our results indicated that the Dax-1 gene is regulated by Ad4BP.Nevertheless, thedistribution was not identical to that of Ad4BP,indicating that unknown transcription factors in addition to Ad4BP are probably needed for the transcription of the Dax-1 gene. Concerning the transcriptional regulation of the P450 genes, negative regulation by DAX-1 should be considered to understand their whole regulation.