title: The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lee
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Han
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
mesh_terms: D000818:Animals; D003656:Decidua / Q000187:drug effects / Q000502:physiology; D004717:Endometrium / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000235:genetics / Q000502:physiology; D006706:Homeostasis; D051379:Mice; D051958:Nuclear Receptor Coactivator 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D056921:Nuclear Receptor Coactivator 3; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014599:Uterus / Q000502:physiology
chemical_list: D051958:Nuclear Receptor Coactivator 2; D015534:Trans-Activators; D011374:Progesterone; D051548:Histone Acetyltransferases; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3