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Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland – involvement of cAMP‐responsive element modulator in epigenetic regulation of Cyp17a1
Author(s) -
Košir Rok,
Zmrzljak Ursula Prosenc,
Bele Tanja,
Acimovic Jure,
Perse Martina,
Majdic Gregor,
Prehn Cornelia,
Adamski Jerzy,
Rozman Damjana
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08317.x
Subject(s) - cyp17a1 , zeitgeber , endocrinology , biology , knockout mouse , cholesterol side chain cleavage enzyme , medicine , adrenal gland , epigenetics , circadian rhythm , cytochrome p450 , gene , circadian clock , genetics , metabolism
The cytochrome P450 (CYP) genes Cyp51 , Cyp11a1 , Cyp17a1 , Cyb11b1 , Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator ( Crem ) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM‐dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands.