THE ROLE OF TRANSCRIPTIONAL REGULATION IN STEROID-HORMONE BIOSYNTHESIS

The regulated expression of the genes encoding the various steroidogenic enzymes is a crucial component in the control of steroid hormone biosynthesis. Tissue-specific transcription of each of the steroidogenic enzyme genes determines the array of enzymes present within a steroidogenic tissue, and therefore the types of steroid hormones the tissue produces. Transcriptional regulation also determines developmental changes in the steroid hormones synthesized by steroidogenic tissues and for the quantitative regulation of steroid hormones necessary for reproduction and for maintaining physiological homeostasis. The molecular mechanisms governing transcriptional regulation of steroidogenic enzyme genes is now being studied. The results so far indicate that, like most other genes, transcription of steroidogenic enzyme genes is regulated by cis-elements in the 5' flanking DNA of the genes that bind trans-acting proteins found in the nucleus. Several types of cis-elements have been identified: elements responsible for basal transcription, for induction by cAMP, and for both basal and cAMP induction. Some of the basal cis-elements identified may have a role in tissue-specific transcription of certain steroidogenic enzyme genes in steroidogenic tissues. We have also identified regions in both the human P450scc and human P450c17 promoters that repress transcription when activated by the Ca2+/protein kinase C intracellular second messenger system used by angiotensin II. This review summarizes our current understanding of transcriptional regulation of the steroidogenic enzyme genes.