孕激素对子宫内膜上皮细胞增殖调控机制研究进展

Research Progress in Proliferation Regulation by Progestogen on Endometrial Epithelial Cells

子宫内膜是卵巢激素的主要靶器官,女性进入青春期后,在下丘脑垂体的调节下,雌激素、孕激素出现周期性分泌,子宫内膜的形态和功能也随之发生改变.黄体期,血清中上升的孕激素可拮抗雌激素的作用,抑制子宫内膜上皮细胞的增殖,使其分化为具有分泌功能的上皮细胞.孕激素抑制子宫内膜上皮细胞增殖并促使其分化的机制主要是:一方面孕激素通过降低子宫内膜上皮细胞雌激素受体(ER)的表达,降低颗粒细胞分泌细胞色素P450芳香化酶的表达和活性,增加17β-HSDII在子宫内膜局部的表达和活性,增强雌激素代谢,从而抑制雌激素对子宫内膜上皮细胞的促增殖作用,间接抑制子宫内膜上皮细胞的增殖;另一方面孕激素通过与子宫内膜上皮细胞的孕激素受体结合后进入核内,调节细胞周期调控蛋白、原癌基因等参与细胞周期调控的分子表达,直接抑制子宫内膜上皮细胞的增殖并促使其分化.

Endometrium is a major target organ of ovarian hormones. After puberty, under the regulation of hypothalamus-pituitary, with cyclical secretion of estrogen and progestogen, endometrial morphology and function also will be changed.In luteal phase,progestogen antagonizes the effect of estrogen to inhibit the proliferation of endometrial epithelial cells, and promotes them to differentiate into secretory ceils. Progestogen suppresses proliferation of endometrial epithelial cells and promotes them to differentiation, its mechanism plays a role in two aspects. On the one hand, progesterone can reduce estrogen receptor （ER） expression in endometrial epithelial cells; and reduce the expression and activity of cytochrome P450 aromatase in granulosa cells and increase 17β-HSDII local expression and activity in endometrium for enhancing estrogen mefitbolism. Thereby, progesterone can indirectly inhibit the proliferation of endometrial epithelial cells. On the other hand, progesterone combines with progesterone receptor, then gets into endometrial epithelial cells＇ nucleus, regulating expression of cell cycle regulatory proteins, proto-oncogenes and other molecules involved in cell cycle regulation, with directly inhibits the proliferation of endometrial epithelial cells and promotes their differentiation.