Binding of Steroidogenic Factor-1 to the Regulatory Region Might Not Be Critical for Transcriptional Regulation of the Human CYP1B1 Gene

Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192.
Journal of Biochemistry (Impact Factor: 2.58). 04/2006; 139(3):527-34. DOI: 10.1093/jb/mvj055
Source: PubMed


Cytochrome P450 (CYP) 1B1, which catalyzes 17β-estradiol 4-hydroxylation, is expressed in steroid-related tissues including
ovary, testis, and adrenal gland. Generally, the expressions of steroidogenic CYPs are transcriptionally regulated by steroidogenic
factor-1 (SF-1) and cAMP response element (CRE) binding protein (CREB). In the present study, we examined the possibility
that the human CYP1B1 gene might be regulated by SF-1 and CREB. Gel shift analyses revealed that in vitro translated SF-1 can bind to the putative SF-1 binding sites, SF-1a (at –1722) and SF-1b (at –2474), on the CYP1B1 gene. In vitro translated CREB barely binds to the putative SF-1 binding sites. Luciferase analysis revealed that a reporter plasmid, pGL3
(–2623/+25), containing the SF-1a and SF-1b elements is transactivated by the concomitant co-expression of SF-1 and protein
kinase A (PKA). However, the transcriptional activity is induced by PKA alone. Mutations in the SF-1a and SF-1b elements did
not affect the luciferase activity. Thus, the binding of SF-1 to the putative SF-1 binding sites of the human CYP1B1 gene might not be essential for transcriptional regulation. Interestingly, deletion and mutation analyses indicated that
the PKA signaling pathway is involved in the xenobiotic responsive element (XRE)–mediated transactivation of the human CYP1B1 gene.

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