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Transcription of the Human Genes for Cytochrome P450scc and P450c17 Is Regulated Differently in Human Adrenal NCI-H295 Cells Than in Mouse Adrenal Y1 Cells¹

Department of Pediatrics and the Metabolic Research Unit, University of California, San Francisco, California 94143-0978

Address all correspondence to and requests for reprints to: Dr. Walter L. Miller, Building MR IV, Room 209, University of California, San Francisco, California 94143-0978.

Human NCI-H295 cells, which express all of the genes for the steroidogenic enzymes in a hormonally regulated fashion, should be an ideal system in which to study the transcriptional regulation of these genes. Using deletional promoter/reporter constructions for the human P450scc and P450c17 genes, we identified the regions conferring basal and cAMP-induced transcription of these two genes in NCI-H295 human adrenal cells. In the P450scc gene, both basal and cAMP-induced transcriptional activation elements lie within the first 79 bp upstream (-79) from the transcriptional start site. In the P450c17 promoter, both basal and cAMP-responsive elements lie within the first upstream 63 bp, and a second basal element lies between -184 and -206 bp. The locations of these elements are substantially different from the locations of elements that appear to be functionally equivalent when these human gene promoters are transfected into mouse adrenal Y1, mouse testicular MA-10, or human choriocarcinoma JEG-3 cells. These data indicate that the transcriptional regulation of these genes in their native species and cell type differs substantially from their regulation in cells from other species and tissues, and suggests that the results from transfection experiments examining genes for steroidogenic enzymes in heterologous cells may not reflect events in vivo.

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