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E Missaghian, Dept. of Paediatric Endocrinology and Diabetology, University Childrens Hospital Inselspital, Bern, Switzerland
P Kempna, Pediatric Endocrinology and Diabetology, University of Bern, Bern, Switzerland
B Dick, Inselspital, Univ of Bern, Department of Nephrology and Hypertension, Bern, Switzerland
A Hirsch, Dept. of Paediatric Endocrinology and Diabetology, University Childrens Hospital Inselspital, Bern, Switzerland
R Alikhani-Koupaei, Inselspital, Univ of Bern, Department of Nephrology and Hypertension, Bern, Switzerland
B Jegou, Inserm, U625, GERHM, IFR140, University of Rennes, Rennes Cedex, France
P Mullis, Dept. of Paediatric Endocrinology and Diabetology, University Childrens Hospital Inselspital, Bern, Switzerland
B Frey, Inselspital, Univ of Bern, Department of Nephrology and Hypertension, Bern, Switzerland
C Fluck, Dept. of Paediatric Endocrinology and Diabetology, University Childrens Hospital Inselspital, G3 812, Berne, Switzerland

Correspondence: Christa Fluck, Email: christa.flueck{at}insel.ch

The CYP17 gene is the qualitative regulator of steroidogenesis. Depending on the presence or absence of CYP17 activities mineralocorticoids, glucocorticoids or adrenal androgens are produced. The expression of the CYP17 gene is tissue- as well as species-specific. In contrast to humans, adrenals of rodents do not express the CYP17 gene and have therefore no P450c17 enzyme for cortisol production, but produce corticosterone. DNA methylation is involved in the tissue-specific silencing of the CYP17 gene in human placental JEG3 cells. We investigated the role of DNA methylation for the tissue-specific expression of the CYP17 gene in rodents. Rats treated with the methyltransferase inhibitor 5-aza-deoxycytidine excreted the cortisol metabolite tetrahydrocortisol in the urine suggesting that treatment induced CYP17 expression and 17-hydroxylase activity through demethylation. Accordingly, bisulfite modification experiments identified a methylated CpG island in the CYP17 promoter in DNA extracted from rat adrenals but not from testes. Both methyltransferase and histone deacetylase inhibitors induced the expression of the CYP17 gene in mouse adrenocortical Y1 cells which normally do not express CYP17, indicating that the expression of the mouse CYP17 gene is epigenetically controlled. The role of DNA methylation for CYP17 expression was further underlined by the finding that a reporter construct driven by the mouse -1041bp CYP17 promoter was active in Y1 cells, thus excluding the lack of essential transcription factors for CYP17 expression in these adrenal cells.