Etv5, an ETS transcription factor, is expressed in granulosa and cumulus cells and serves as a transcriptional regulator of the cyclooxygenase-2

J Endocrinol. 2008 Aug;198(2):281-90. doi: 10.1677/JOE-08-0142. Epub 2008 May 20.

Abstract

Etv4, Etv1, and Etv5 are members of Etv4 subfamily of E26 transformation-specific (Ets) transcription factors that are known to influence a host of biological processes. We previously showed that Etv5, expressed in Sertoli cells, plays a crucial role in maintaining spermatogonial stem cell niche in the mouse testis. However, it is not yet known whether Etv4 family members are expressed in the ovary or play any role in ovarian functions. Here, we show that Etv5 and Etv4 are expressed in mouse ovaries in granulosa and cumulus cells during folliculogenesis. Both Etv5 and Etv4 mRNAs are also detected in cumulus-oocyte complexes (COCs) and denuded oocytes. Notably, Etv4 is highly expressed in the cumulus cells of ovulated COCs at 16-h post-human chorionic gonadotropin. Cyclooxygenase-2 (PTGS2), a rate-limiting enzyme for prostaglandin synthesis, is critical for oocyte maturation and ovulation. Since several putative Ets-binding sites are present in the PTGS2 promoter, we examined whether Etv5 influences Ptgs2 transcriptional activity. Indeed, we found that addition of Etv5 increases the transcriptional activity of the 3.2-kb mouse Ptgs2 promoter by 2.5-fold in luciferase reporter assays. Collectively, the results show that Etv4 and Etv5 are expressed in granulosa and cumulus cells during folliculogenesis and ovulation, suggesting that they influence cellular events in the ovary by regulating downstream genes such as Ptgs2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chorionic Gonadotropin / pharmacology
  • Cumulus Cells / drug effects
  • Cumulus Cells / metabolism*
  • Cyclooxygenase 2 / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Combinations
  • Female
  • Fluorescent Antibody Technique
  • Gonadotropins, Equine / pharmacology
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • In Vitro Techniques
  • Mice
  • Microscopy, Confocal
  • Ovary / drug effects
  • Ovary / metabolism
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Chorionic Gonadotropin
  • DNA-Binding Proteins
  • Drug Combinations
  • Etv1 protein, mouse
  • Etv4 protein, mouse
  • Etv5 protein, mouse
  • Gonadotropins, Equine
  • PMSG-HCG
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2