cAMP-dependent regulation of CYP19 gene in rabbit preovulatory granulosa cells and corpus luteum

Thomas Andrieu, Vincenzo Pezzi, Rosa Sirianni, Raluca Le Bas, Colette Feral, Annie Benhaim, Hervé Mittre

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Transcription of the CYP19 gene encoding the aromatase P450 enzyme in ovarian cells is under the control of the two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), via modulation of intracellular cyclic 3′,5′-adenosine monophosphate (cAMP) levels. Primary cultures of rabbit ovarian cells were used to identify the functional regions of the ovarian promoter (PII) that are responsive to the gonadotropic secondary messenger and to estradiol. Transfection experiments in granulosa and luteal cells with deleted constructs of the PII promoter show that the region between -274 and -193 bp is critical for cAMP-dependent transcriptional activity. A comparison of PII activities in granulosa and small luteal cells highlights a 50% decrease consecutive to the LH surge. Sequence analysis of the above mentioned region revealed the presence of a cAMP responsive element like sequence (CLS) and of a nuclear receptor element A (NREA). Binding of CREB to CLS has been shown using granulosa and luteal cells nuclear extracts. In addition, we identified the expression of NR5A1 (Steroidogenic Factor 1) and NR5A2 (Liver Receptor Homologue 1) in granulosa and luteal cells. However, the binding to NREA is observed only with granulosa cells nuclear extracts. Data suggest that the NR5A factors are not the main regulators of CYP19 gene, in contrast with the others genes of streroidogenesis enzymes, and additional sites may play an important role during the post-LH surge down-regulation of CYP19 transcription.

Original languageEnglish (US)
Pages (from-to)110-117
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume116
Issue number1-2
DOIs
StatePublished - Aug 2009

Keywords

  • Aromatase
  • CRE
  • CYP19
  • LRH1
  • Luteal cells
  • SF1
  • cAMP

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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