THE TESTIS AND THE ADRENAL ARE (TRANSCRIPTIONALLY) THE SAME

We have been studying the transcriptional regulation of the rat P450c1 7 gene in both adrenocortical and Leydig cells. to assess which DNA se quences are required for its basal and hormonally stimulated transcrip tion Comparing the transcriptional regulation in both of these cell ty pes enables us to demonstrate whether specific nuclear factors require d for transcriptional regulation of the rat P450c17 gene are tissue-sp ecifically expressed, and whether the same cis-acting DNA elements in the gene are required for transcriptional regulation in both of these two different steroidogenic tissues. Using such an approach, we previo usly demonstrated that the transcriptional regulation of the rat P450s cc gene uses different cis-acting DNA sequences in steroidogenic versu s neural tissues, and requires the expression of tissue-specific nucle ar factors that are unique to neural tissue. However, in studying the transcriptional regulation of the rat P450c17 gene in cultured mouse a drenocortical Y-1 and mouse Leydig MA-10 cells, we have shown that ide ntical DNA sequences necessary for basal and cAMP stimulated transcrip tional regulation in these two cell types, and that identical nuclear factors from Y-1 and from MA-10 cells bind to these sequences. We have identified four transcriptional active regions within 500 bp of the t ranscription initiation start site that are important for basal and/or cAMP-stimulated transcriptional regulation of this gene in Y-1 and MA -10 cells. This paper will discuss two of these regions in greater det ail. By studying the regulation of the rat P450c17 gene, we have ident ified two new members of the orphan nuclear receptor gene family and h ave discovered new alternative mechanisms by which orphan nuclear rece ptors activate gene transcription in both mouse adrenocortical Y-1 and Leydig MA-10 cells. (C) 1997 by Elsevier Science Inc.