17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis.
17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis.
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DOI：
10.1055/s-0029-1242992
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发表时间：
2010-01-01
影响因子：
2.7
通讯作者：
Su, Emily J
中科院分区：
文献类型：
--
作者：
Bulun, Serdar E;Cheng, You-Hong;Su, Emily J
雌二醇（E2）刺激子宫内膜异位组织的生长和炎症，通常位于盆腔器官上。一些基于临床和实验室的观察表明子宫内膜异位症对黄体酮的抵抗作用。子宫内膜异位症中黄体酮抵抗的分子基础可能与黄体酮受体（PR）水平的整体降低有关。在正常子宫内膜中，孕酮通过PR作用于基质细胞，诱导分泌旁分泌因子，进而刺激邻近上皮细胞表达酶17β -羟基类固醇脱氢酶2 （HSD17B2）。HSD17B2是一种非常有效的酶，能将生物活性强的雌激素E2迅速代谢为弱雌激素酮。在子宫内膜异位症组织中，由于基质细胞的缺陷，黄体酮无法诱导上皮细胞HSD17B2的表达。子宫内膜异位症间质细胞不能产生刺激HSD17B2的孕激素诱导的旁分泌因子，可能是由于在体内子宫内膜异位症组织中观察到的PR水平非常低。最终的结果是E2在子宫内膜异位症中代谢不足，引起局部高浓度的有丝分裂原。本文讨论了正常子宫内膜间质和上皮之间的生理旁分泌相互作用及其在子宫内膜异位症中缺乏的分子细节。
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.