The testis and the adrenal are (transcriptionally) the same

Abstract

We have been studying the transcriptional regulation of the rat P450c17 gene in both adrenocortical and Leydig cells, to assess which DNA sequences are required for its basal and hormonally stimulated transcription. Comparing the transcriptional regulation in both of these cell types enables us to demonstrate whether specific nuclear factors required for transcriptional regulation of the rat P450c17 gene are tissue-specifically 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 previously demonstrated that the transcriptional regulation of the rat P450scc gene uses different cis-acting DNA sequences in steroidogenic versus neural tissues, and requires the expression of tissue-specific nuclear factors that are unique to neural tissue. However, in studying the transcriptional regulation of the rat P450c17 gene in cultured mouse adrenocortical Y-1 and mouse Leydig MA-10 cells, we have shown that identical DNA sequences necessary for basal and cAMP-stimulated transcriptional 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 transcriptionally active regions within 500 bp of the transcription 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 detail. By studying the regulation of the rat P450c17 gene, we have identified two new members of the orphan nuclear receptor gene family and have discovered new alternative mechanisms by which orphan nuclear receptors activate gene transcription in both mouse adrenocortical Y-1 and Leydig MA-10 cells.