Transcriptional regulation of the gene encoding the StAR protein in the human adrenocortical cell line, H295R by cAMP and TGFβ1

In the present work, we have analyzed the transcriptional regulation of StAR expression in the human adrenocortical cell line H295R. We observed that StAR mRNA levels rapidly increased in response to forskolin, starting after 2 h of treatment and reaching a maximum by 12 h. Deletion analysis of the human StAR promoter demonstrated that the first 150 bp upstream of the transcription start were sufficient for both basal and cAMP-induced expression of a reporter gene. We demonstrate that out of the three binding sequences for the steroidogenic factor 1 (SF-1) only the central one (-105 to -96) is implicated in both basal and cAMP-induced StAR expression. In addition, another important regulatory element for both basal and cAMP-induced StAR expression is present between -62 and -24 upstream of the transcription start. We also show that TGF beta1 inhibits StAR expression at the transcriptional level. We found that the TGF beta -inhibitory element lies between -150 and -85 upstream of the transcription start and that the SF-1 binding sites are not implicated in TGF beta1 regulation.