Division of Reproductive Biology Research, Department Obstetrics and Gynecology Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Semin Reprod Med. 2010 Jan;28(1):44-50. doi: 10.1055/s-0029-1242992.
Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.
雌二醇（E2）刺激异位子宫内膜组织的生长和炎症，这些组织通常位于盆腔器官上。一些临床和实验室的观察表明，子宫内膜异位症对孕激素作用有抗性。子宫内膜异位症中孕激素抗性的分子基础可能与孕激素受体（PR）水平整体降低有关。在正常子宫内膜中，孕激素通过 PR 作用于基质细胞，诱导旁分泌因子的分泌，而这些旁分泌因子反过来又刺激邻近的上皮细胞表达酶 17β-羟类固醇脱氢酶 2（HSD17B2）。HSD17B2 是一种非常有效的酶，可迅速将生物活性强的雌激素 E2 代谢为弱雌激素雌酮。在异位子宫内膜组织中，由于基质细胞存在缺陷，孕激素无法诱导上皮细胞 HSD17B2 的表达。由于在体内观察到异位子宫内膜组织中 PR 水平极低，因此，异位子宫内膜组织中的基质细胞无法产生孕激素诱导的旁分泌因子来刺激 HSD17B2。其结果是 E2 的代谢不足，导致这种有丝分裂原在局部的浓度升高。本文讨论了正常子宫内膜中基质和上皮之间这种生理性旁分泌相互作用的分子细节，以及其在子宫内膜异位症中的缺失。
