1. The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression.
- Author
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Jeong JW, Lee KY, Han SJ, Aronow BJ, Lydon JP, O'Malley BW, and DeMayo FJ
- Subjects
- Animals, Decidua drug effects, Decidua physiology, Female, Histone Acetyltransferases genetics, Histone Acetyltransferases physiology, Homeostasis, Mice, Nuclear Receptor Coactivator 2 deficiency, Nuclear Receptor Coactivator 2 genetics, Nuclear Receptor Coactivator 3, Ovariectomy, Polymerase Chain Reaction, Pregnancy, Progesterone pharmacology, Trans-Activators genetics, Trans-Activators physiology, Uterus physiology, Endometrium physiology, Gene Expression Regulation drug effects, Nuclear Receptor Coactivator 2 physiology, Progesterone physiology
- Abstract
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.
- Published
- 2007
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