Shiozawa Tanri, Shih Hsien-Chang, Miyamoto Tsutomu, Feng Yu-Zhen, Uchikawa Junko, Itoh Kazuko, Konishi Ikuo
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
J Clin Endocrinol Metab. 2003 Feb;88(2):871-8. doi: 10.1210/jc.2002-020946.
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.
为研究人子宫内膜的性类固醇依赖性生长机制，采用免疫组织化学方法，检测了50例正常子宫内膜样本中类固醇受体共激活因子[类固醇受体共激活因子-1（SRC-1）和p300/CREB结合蛋白（p300/CBP）]及共抑制因子（核受体共抑制因子和视黄酸及甲状腺激素受体沉默介质）的表达，并与雌激素受体（ER）、孕激素受体（PR）及增殖标志物Ki-67的表达进行比较。此外，通过免疫沉淀分析共激活因子与ER或PR的实际结合情况。SRC-1的表达在增殖期的腺细胞和基质细胞中呈弥漫性，在分泌期急剧下降。SRC-1表达模式的这种变化与ER、PR和Ki-67的相似。另一方面，p300/CBP的表达在整个月经周期相对恒定，在增殖期略有优势。共抑制因子核受体共抑制因子和视黄酸及甲状腺激素受体沉默介质的表达在子宫内膜中呈局灶性。使用增殖期和分泌期的组织样本进行免疫沉淀，结果显示共激活因子与受体之间形成复合物。在增殖期（而非分泌期）子宫内膜中观察到SRC-1与ER的结合。相反，在两个阶段的子宫内膜中均检测到p300/CBP与ER的结合。在分泌期子宫内膜中发现p300/CBP与PR形成复合物，而SRC-1与PR之间未观察到明显结合。因此，我们展示了正常子宫内膜中类固醇受体共激活因子和共抑制因子的表达模式。月经周期中SRC-1表达的周期性变化可能对腺细胞和基质细胞的雌激素作用至关重要。
