Action of hormone responsive sequence in 2.3 kb promoter of CYP11A1

The CYP11A1 gene encodes cytochrome P450scc, the enzyme catalyzing the firs t step of steroid biosynthesis in the adrenal and gonad. We generated trans genic mice containing 2.3 kb of the 5'-flanking region of CYP11A1 driving L acZ reporter gene expression, in order to study hormonal control of CYP11A1 gene expression in different tissues. This 2.3 kb fragment contains inform ation for hormonal control; by ACTH and hCG which increased reporter gene e xpression, in the adrenal and testis of transgenic mice respectively, while dexamethasone administration decreased reporter activity in the adrenal. T he 5'-fragment of CYP11A1 has appreciable promoter activities in mouse adre nal Y1 cells but not in non-steroidogenic COS-1 cells: showing cell-type sp ecificity. Transcription factor SF-1 activates the 2.3 kb promoter, which c an be potentiated by cotransfection with c-Jun in steroidogenic JEG3 cells but not in COS-1 cells. We conclude that the 2.3 kb region of CYP11A1 conta ins elements controlling hormonal-dependent, cell-type-specific expression. In addition, c-jun and SF-1 could act synergistically to activate CYP11A1 gene expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .