The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

Biochem Biophys Res Commun. 2011 Jan 14;404(2):628-33. doi: 10.1016/j.bbrc.2010.12.027. Epub 2010 Dec 10.

Abstract

Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Cells, Cultured
  • Decidua / metabolism*
  • Endometrium / metabolism
  • Female
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Humans
  • Luciferases / genetics
  • Medroxyprogesterone Acetate / pharmacology
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Prolactin / genetics*
  • Promoter Regions, Genetic
  • Stromal Cells / metabolism
  • Up-Regulation

Substances

  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Prolactin
  • Medroxyprogesterone Acetate
  • Luciferases