Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA.
Biol Reprod. 2012 Mar 22;86(3):78. doi: 10.1095/biolreprod.111.095588. Print 2012 Mar.
The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG). Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from equine CG (eCG)-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells, but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone receptor antagonist RU486 suppressed the induction of Mmp10 mRNA, whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated that forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation, with a marked induction of Mmp10 mRNA and a decrease in Mmp11 mRNA, yet a species-dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization.
基质金属蛋白酶（MMPs）被认为有助于卵泡破裂。在本研究中，分析了基质溶解素（MMP3、MMP10、MMP11）在人及大鼠排卵周期中的表达。人颗粒细胞和膜细胞是在 hCG 注射后不同时间从优势卵泡中采集的。从 eCG-hCG 预处理的动物中分离出完整的大鼠卵巢、颗粒细胞和剩余组织（颗粒细胞收集后残留的组织）。Mmp10mRNA 在人颗粒细胞和膜细胞以及完整的大鼠卵巢、颗粒细胞和剩余组织中高度诱导。免疫组化证实 MMP10 定位于人及大鼠卵巢卵泡中的颗粒细胞和膜细胞。Mmp3mRNA 在人细胞和大鼠颗粒细胞中没有变化，但在完整的大鼠卵巢和剩余组织中增加。Mmp11mRNA 在 hCG 处理后人颗粒细胞和膜细胞以及大鼠颗粒细胞中减少。在培养的大鼠颗粒细胞中对 Mmp10 的调控研究表明，EGF 抑制剂 AG1478 和孕激素受体拮抗剂 RU486 抑制了 Mmp10mRNA 的诱导，而前列腺素抑制剂 NS398 没有作用。对 Mmp10 启动子的研究表明，forskolin plus PMA 刺激启动子活性，这依赖于近端的 AP1 位点。总之，与排卵相关的基质溶解素表达存在不同的模式，Mmp10mRNA 的诱导明显，Mmp11mRNA 的减少，但 Mmp3mRNA 表达存在种属依赖性。Mmp10 表达的诱导表明该 MMP 在与排卵和随后的黄体化相关的卵泡变化中具有重要作用。
