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Cyclic Changes in the Expression of Steroid Receptor Coactivators and Corepressors in the Normal Human Endometrium

Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan

Address all correspondence and requests for reprints to: Tanri Shiozawa, M.D., Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. E-mail: tanri{at}hsp.md.shinshu-u.ac.jp.

To examine the sex steroid-dependent growth mechanisms of the human endometrium, the expression of steroid receptor coactivators [steroid receptor coactivator-1 (SRC-1) and p300/CREB-binding protein (p300/CBP)] and corepressors (nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors) was examined by immunohistochemistry, using 50 samples of normal endometria, and was compared with that of estrogen receptors (ER), progesterone receptors (PR), and proliferation marker Ki-67. In addition, actual binding of the coactivators to ER or PR was analyzed by immunoprecipitation. The expression of SRC-1 was diffusely observed in glandular and stromal cells in the proliferative phase and drastically decreased in the secretory phase. Such change in the expression pattern of SRC-1 resembled that of ER, PR, and Ki-67. On the other hand, p300/CBP expression was relatively constant throughout the menstrual cycle, with slight predominance in the proliferative phase. The expression of corepressors nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors was focal in the endometrium. Immunoprecipitation, using tissue samples of both proliferative and secretory phases, revealed the complex formation between the coactivators and receptors. Binding of SRC-1 to ER was observed in the proliferative (but not in the secretory) endometrium. In contrast, binding p300/CBP to ER was noted in the endometria of both phases. Complex formation between p300/CBP and PR was noted in the secretory endometrium, whereas that between SRC-1 and PR was not apparent. Accordingly, we showed the expression pattern of steroid receptor coactivators and corepressors in the normal endometrium. Cyclic change in the expression of SRC-1 during the menstrual cycle might be important in the estrogen-action for the glandular and stromal cells.

This work was supported in part by Grants-in-Aid for Scientific Research (06454468 and 07807154) from the Ministry of Education, Science and Culture, Japan.

Abbreviations: CBP, CREB-binding protein; CREB, cAMP-response element binding protein; ER, estrogen receptor(s); NCoR, nuclear receptor corepressor; PI, positivity index; PR, progesterone receptor(s); SDS, sodium dodecyl sulfate; SMRT, silencing mediator for retinoid and thyroid hormone receptors; SRC, steroid receptor coactivator; TBST, Tris-buffered saline with Tween 20.

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