The role and significance of endomorphin-1 and μ-opioid receptor in rats with endometriosis

Abstract

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.

Chinese abstract

据报道, 内啡肽-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, 仍不清楚EM-1和MOR是否参与子宫内膜异位症的病理学、导致生育力降低。在本研究中, 分别使用RT-PCR, 放射免疫测定, 免疫组织化学和Western印迹。结果显示, 子宫内膜异位模型大鼠下丘脑、垂体和卵巢中EM-1的免疫阳性细胞明显增多, 伴有血浆EM-1水平的升高和卵泡刺激素 (FSH) 、促黄体激素 (LH) 、雌二醇 (E2) 和孕酮 (P) 的减少。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) 可以显着降低血清、下丘脑、垂体和卵巢中的EM-1水平, 同时增加FSH和LH水平。总之, 我们的研究结果表明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不孕症的发病机制, 纳洛酮可能是一种新的治疗子宫内膜异位症的替代药物。

Keywords:

• Endometriosis
• endomorphin-1
• gonadal hormone
• infertile
• MOR

Declaration of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

This study was supported by Grants from the National Natural Science Foundation of China (No. 81560254 and 81560143), Scientific research projects of Health care industry in Gansu province in 2014 (GWGL2014-55 and 2014-59).