Progesterone-action in the murine uterus and mammary gland requires steroid receptor coactivator 2: relevance to the human.
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 (PRCre/+SRC-2flox/flox) was generated in which SRC-2 function was ablated specifically in cell-types that express the PR. Although PRCre/+SRC-2flox/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 PRCre/+SRC-2flox/flox uterus can display a partial decidual response, removal of SRC-1 in the PRCre/+SRC-2flox/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 PRCre/+SRC-2flox/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.
Fernandez-Valdivia
Rodrigo
R
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Mukherjee
Atish
A
Amato
Paula
P
Allred
D Craig
DC
Nguyen
Jonathan
J
DeMayo
Francesco J
FJ
Lydon
John P
JP
D000818:Animals; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D051958:Nuclear Receptor Coactivator 2 / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D014599:Uterus / Q000502:physiology*
D051958:Nuclear Receptor Coactivator 2; D011374:Progesterone