REGULATION OF EXPRESSION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN (STAR) GENE - A CENTRAL ROLE FOR STEROIDOGENIC FACTOR-1

Steroidogenic acute regulatory protein (StAR) plays a critical role in regulating the rate-limiting step in steroid hormone synthesis, chole sterol side-chain cleavage. StAR gene expression is transcriptionally controlled in the gonads by gonadotropic hormones via a cAMP second me ssage. We have begun to analyze factors responsible for the transcript ional activation of the StAR gene. The human SrAR gene promoter has at least two cis elements that govern basal and cAMP-regulated gene expr ession. One of these elements (the distal element) is a consensus bind ing sequence for the orphan nuclear receptor transcription factor, ste roidogenic factor 1 (SF-1); the other (the proximal element) is a rela ted motif. The human StAR promoter is not active in BeWo choriocarcino ma cells, but is functional and cAMP-responsive in murine Y1 adrenal c ortical tumor cells. Cotransfection of a plasmid expressing SF-1 allow s a StAR promoter construct to function in BeWo cells. Other orphan nu clear transcription factors do not support StAR promoter function in B eWo cell hosts. Deletion or mutation of the distal and proximal cis el ements individually substantially reduces SF-1-supported StAR promoter activity The distal site binds SF-1 with high affinity whereas the pr oximal site binds SF-1 with lower affinities. These findings demonstra te a requirement for SF-1 for human StAR gene expression. (C) 1997 by Elsevier Science Inc.