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

FEBS J. 2012 May;279(9):1584-93. doi: 10.1111/j.1742-4658.2011.08317.x. Epub 2011 Sep 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / metabolism*
  • Animals
  • Circadian Rhythm
  • Corticosterone / blood
  • Cyclic AMP Response Element Modulator / genetics
  • Cyclic AMP Response Element Modulator / metabolism*
  • 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*

Substances

  • Cyclic AMP Response Element Modulator
  • Steroid 17-alpha-Hydroxylase
  • Corticosterone