Ranjbaran Javad, Farimani Marzieh, Tavilani Heidar, Ghorbani Marzieh, Karimi Jamshid, Poormonsefi Faranak, Khodadadi Iraj
Department of BiochemistryFaculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranEndometrium and Endometriosis Research CentreFatemieh Hospital, Hamadan, Iran.
Reproduction. 2016 Apr;151(4):305-11. doi: 10.1530/REP-15-0340. Epub 2016 Jan 5.
It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.
据信，基质金属蛋白酶（MMPs）在卵泡发育和多囊卵巢综合征（PCOS）的发病机制中起重要作用。然而，关于PCOS中MMP2和MMP9浓度或活性的改变，存在相互矛盾的结果。事实上，尚无研究全面调查这些MMPs的浓度和活性及其组织抑制剂TIMP2和TIMP1的血清水平，以及MMP9的脂质运载蛋白结合形式（MMP9/NGAL）。因此，先前研究的全面性值得怀疑。本研究旨在测定PCOS女性和对照组中MMP2、MMP9、MMP9/NGAL复合物、TIMP1和TIMP2的循环浓度，以及MMP2、MMP9和MMP9/NGAL复合物的明胶酶活性。两组之间的平均年龄、BMI以及总胆固醇、三酰甘油、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FBS）、胰岛素、雌二醇和性激素结合球蛋白的血清水平无差异，而促卵泡生成素（FSH）显著降低，促黄体生成素（LH）、LH/FSH比值、睾酮和游离雄激素指数显著升高。PCOS女性和对照组的MMP2、MMP9、MMP9/NGAL、TIMP1和TIMP2浓度相近。发现PCOS中MMP9的明胶酶活性显著高于对照组（分别为64.53±15.32和44.61±18.95），而患者和健康受试者的MMP2和MMP9/NGAL复合物活性相似。此外，与对照女性相比，PCOS患者的MMP9/TIMP1比值更高。循环MMP9水平与MMP9/NGAL复合物的浓度和活性之间也存在直接相关性。总之，基于本研究结果，我们认为MMP9可能参与PCOS的发病机制。
