Function of Ad4BP in the process of gonadal sex differentiation

免疫组织化学分析与抗Ad 4 BP显示，性腺和肾上腺皮质，主要的类固醇激素产生组织，是来自同一个细胞群。Ad 4 BP免疫阳性细胞分为两个群体，然后产生性腺和肾上腺皮质的原基。在这一过程中，一个有趣的问题是为什么性分化发生在性腺而不是在肾上腺皮质发育。本研究对性腺性别分化的机制进行了探讨，并对转录因子Ad 4 BP和DAX-1的表达和功能进行了广泛的研究。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Ad 4 BP阳性细胞并不总是DAX-1阳性。这两个转录因子之间的这种不同的表达被认为是在11.5 dpc小鼠胎儿的生殖嵴。在DAX-1的功能方面，DAX-1抑制腺病毒4 BP激活的类固醇合成P450基因的转录，而DAX-1 ge的转录受腺病毒4 BP的调控，推测DAX-1可能是抑制性腺和肾上腺特异性表达基因的转录。结果表明，Dax-1基因受Ad 4 BP调控，但其分布与Ad 4 BP不同，提示Dax-1基因的转录可能还需要Ad 4 BP以外的未知转录因子。关于P450基因的转录调控，应该考虑DAX-1的负调控，以了解其整体调控。

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.