Function of Ad4BP in the process of gonadal sex differentiation

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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.