Duan Lijun, Wang Jinyang, Sun Xiaotong, Yang Xueping, Shan Long, Liu Yan, Wang Hailin
a Department of Gynecology and Obstetrics and.
b Department of Endocrinology , Gansu Provincial People's Hospital , Lanzhou , PR China.
Gynecol Endocrinol. 2016 Nov;32(11):912-915. doi: 10.1080/09513590.2016.1190816. Epub 2016 Jun 2.
Endomorphin-1 (EM-1) was reported to have very high affinity and selectivity for μ-opioid receptor (MOR). However, it remained unclear whether EM-1 and MOR were involved in the pathologies of endometriosis resulting in reduced fertility. In this study, RT-PCR, radioimmunoassay, immunohistochemistry, and Western blot were used, respectively. The results showed that the immune positive cells of EM-1 in hypothalamus, pituitary, and ovaries were significantly increased in endometriosis model rats, accompanied by the increase of plasma level of EM-1 and the decrease of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). Interestingly, EM-1 was negatively correlated with FSH and LH (p < 0.05). More importantly, Naloxone (MOR antagonist) can significantly reduce the levels of EM-1 in serum, hypothalamus, pituitary, and ovaries, while increased the levels of FSH and LH. In conclusion, our results suggested that EM-1 may be involved in the pathogenesis of the endometriosis-associated infertility by regulating hypothalamus-pituitary-ovarian axis, and Naloxone may be a new alternative drug for the treatment of endometriosis.
据报道,内吗啡肽-1(EM-1)对μ-阿片受体(MOR)具有非常高的亲和力和选择性。然而,EM-1和MOR是否参与导致生育力降低的子宫内膜异位症的病理过程仍不清楚。在本研究中,分别使用了逆转录聚合酶链反应(RT-PCR)、放射免疫测定、免疫组织化学和蛋白质印迹法。结果显示,子宫内膜异位症模型大鼠下丘脑、垂体和卵巢中EM-1的免疫阳性细胞显著增加,同时血浆EM-1水平升高,促卵泡生成素(FSH)、促黄体生成素(LH)、雌二醇(E2)和孕酮(P)水平降低。有趣的是,EM-1与FSH和LH呈负相关(p<0.05)。更重要的是,纳洛酮(MOR拮抗剂)可显著降低血清、下丘脑、垂体和卵巢中EM-1的水平,同时提高FSH和LH的水平。总之,我们的结果表明,EM-1可能通过调节下丘脑-垂体-卵巢轴参与子宫内膜异位症相关性不孕的发病机制,纳洛酮可能是治疗子宫内膜异位症的一种新的替代药物。