Progesterone-action in the murine uterus and mammary gland requires steroid receptor coactivator 2: Relevance to the human

Rodrigo Fernandez-Valdivia, Atish Mukherjee, Paula Amato, D. Craig Allred, Jonathan Nguyen, Francesco J. De Mayo, John P. Lydon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The importance of the progesterone receptor (PR) in female reproductive and mammary gland biology is well recognized; however, the coregulators selectively enlisted by PR have yet to be comprehensively defined in vivo. To evaluate the involvement of steroid receptor coactivator (SRC)/p160 family members in these physiological systems, a mouse model (PR Cre/+SRC-2 flox/flox) was generated in which SRC-2 function was ablated specifically in cell-types that express the PR. Although PR Cre/+SRC- 2 flox/flox ovarian activity was normal, uterine function was severely compromised. Absence of SRC-2 in PR positive uterine cells led to an early block in embryo implantation, a defect not ascribed to SRC-1 or-3 knockouts. While the PR Cre/+SRC-2 flox/flox uterus can display a partial decidual response, removal of SRC-1 in the PR Cre/+SRC-2 flox/flox uterus results in a block in decidualization, confirming that uterine SRC-2 and-1 are both necessary for PR-mediated transcriptional responses which lead to complete decidualization. The absence of significant branching and alveolar morphogenesis in the hormone-treated PR Cre/+SRC-2 flox/flox mammary gland establishes an important role for mammary SRC-2 in cellular proliferative programs that require PR. Finally, the observation that SRC-2 is also expressed in many of the same cell-types in the human, underscores the importance of further study of this coregulator's role in both peri-implantation biology and mammary development.

Original languageEnglish (US)
Pages (from-to)3640-3647
Number of pages8
JournalFrontiers in Bioscience
Volume12
Issue number10
DOIs
StatePublished - May 1 2007
Externally publishedYes

Keywords

  • Branching morphogenesis
  • Decidualization
  • Human
  • Implantation
  • Mammary gland
  • Mouse
  • Progesterone
  • Review
  • Steroid receptor coactivator-2
  • Uterus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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