EGR2 is a gonadotropin-induced survival factor that controls the expression of IER3 in ovarian granulosa cells

Biochem Biophys Res Commun. 2017 Jan 22;482(4):877-882. doi: 10.1016/j.bbrc.2016.11.127. Epub 2016 Nov 24.


Pituitary gonadotropins are key hormones that orchestrate the growth and development of ovarian follicles. However, limited information is available on intra-ovarian factors that mediate the actions of gonadotropins. In this study, we identified that the early growth response 2 gene (EGR2) is a gonadotropin-inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR-binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay, electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation (ChIP), and western blot analysis. Overexpression of EGR2 promoted survival of KGN human granulosa-derived cells in which IER3 acts as a mediator; knockdown of EGR2 induced death in KGN cells. Additionally, EGR2 was found to regulate the expression of myeloid cell leukemia 1 (MCL-1), which belongs to the BCL-2 family of proteins regulating cell survival. Thus, this study identified a novel signaling axis, comprised of gonadotropins-EGR2-IER3, which is important for the survival of granulosa cells during folliculogenesis.

Keywords: FSH; KROX20; LH; Target gene; Transcriptional regulation.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Base Sequence
  • Cell Line
  • Cell Survival
  • Early Growth Response Protein 2 / genetics*
  • Early Growth Response Protein 2 / metabolism
  • Female
  • Gonadotropins / metabolism*
  • Granulosa Cells / cytology
  • Granulosa Cells / metabolism*
  • Humans
  • Membrane Proteins / genetics*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptional Activation*


  • Apoptosis Regulatory Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Egr2 protein, rat
  • Gonadotropins
  • IER3 protein, human
  • IER3 protein, rat
  • Membrane Proteins
  • RNA, Messenger