Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland – involvement of cAMP‐responsive element modulator in epigenetic regulation of Cyp17a1

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...

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Published in:The FEBS journal 2012-05, Vol.279 (9), p.1584-1593
Main Authors: Košir, Rok, Zmrzljak, Ursula Prosenc, Bele, Tanja, Acimovic, Jure, Perse, Martina, Majdic, Gregor, Prehn, Cornelia, Adamski, Jerzy, Rozman, Damjana
Format: Article
Language:English
Subjects:
Adrenal Glands - metabolism
Animals
cAMP‐responsive element modulator (CREM)
circadian
Circadian Rhythm
corticosterone
Corticosterone - blood
Cyclic AMP Response Element Modulator - genetics
Cyclic AMP Response Element Modulator - metabolism
CYP17A1
DNA Methylation
Epigenesis, Genetic - physiology
Gene Expression Regulation, Enzymologic
Mice
Mice, Knockout
Promoter Regions, Genetic
Steroid 17-alpha-Hydroxylase - biosynthesis
Steroid 17-alpha-Hydroxylase - genetics
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Summary: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. By applying cAMP responsive element modulator (Crem) knockout mice we evaluated how CREM isoforms contribute to circadian expression of steroidogenic Cyp51, 11a1, 17a1, 11b1, 11b2 and 21a1 in mouse adrenal glands. Most striking is the CREM dependent hypo‐methylation of Cyp17a1 promoter at zeitgeber time 12 that resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenals.
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2011.08317.x