The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression

Endocrinology. 2007 Sep;148(9):4238-50. doi: 10.1210/en.2007-0122. Epub 2007 Jun 7.


The role of the p160 steroid receptor coactivator 2 (SRC-2) in the regulation of uterine function and progesterone (P4) signaling was investigated by determining the expression pattern of SRC-2 in the murine uterus during pregnancy and the impact of SRC-2 ablation on uterine function and global uterine gene expression in response to progesterone. SRC-2 is expressed in the endometrial luminal and glandular epithelium from pregnancy d 0.5. SRC-2 is then expressed in the endometrial stroma on pregnancy d 2.5-3.5. Once the embryo is implanted, SRC-2 is expressed in the endometrial stromal cells in the secondary decidual zone. This compartmental expression of SRC-2 can be mimicked by treatment of ovariectomized mice with estrogen and P4. Ablation of SRC-2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Microarray analysis of RNA from uteri of wild-type and SRC-2(-/-) mice treated with vehicle or P4 showed that SRC-2 was involved in the ability of progesterone to repress specific genes. This microarray analysis also revealed that the uteri of SRC-2(-/-) mice showed alterations in genes involved in estrogen receptor, Wnt, and bone morphogenetic protein signaling. This analysis indicates that SRC-2 regulates uterine function by modulating the regulation of developmentally important signaling molecules and the ability of P4 to repress specific genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Decidua / drug effects
  • Decidua / physiology
  • Endometrium / physiology*
  • Female
  • Gene Expression Regulation* / drug effects
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / physiology
  • Homeostasis
  • Mice
  • Nuclear Receptor Coactivator 2 / deficiency
  • Nuclear Receptor Coactivator 2 / genetics
  • Nuclear Receptor Coactivator 2 / physiology*
  • Nuclear Receptor Coactivator 3
  • Ovariectomy
  • Polymerase Chain Reaction
  • Pregnancy
  • Progesterone / pharmacology
  • Progesterone / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Uterus / physiology


  • Nuclear Receptor Coactivator 2
  • Trans-Activators
  • Progesterone
  • Histone Acetyltransferases
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3