Institute and Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Sci Rep. 2020 Jan 31;10(1):1576. doi: 10.1038/s41598-020-58125-0.
The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.
药物 17α-乙炔基雌二醇（EE2）被认为是一种内分泌干扰化学物质，可干扰男性生殖和激素激活。在这项研究中，我们研究了 EE2 调节体外和体内睾酮释放的分子机制。结果表明，EE2 处理可减少大鼠睾丸间质细胞的睾酮释放。EE2 处理大鼠可降低血浆睾酮水平并降低人绒毛膜促性腺激素（hCG）的敏感性。EE2 通过下调腺苷酸环化酶活性和减少细胞内钙介导的途径来降低黄体生成素受体（LHR）的表达，从而减少 cAMP 的产生。用 EE2 处理大鼠 7 天可降低 StAR 和 P450scc 的表达。输精管和附睾中的精子运动能力降低，但睾丸的组织病理学特征和输精管中的总精子数不受影响。此外，用 EE2 处理可降低血清中二氢睾酮（DHT）水平。前列腺和精囊明显萎缩，暴露于 EE2 后其 5α-还原酶 II 型的表达水平降低。总之，这些结果表明 EE2 下调睾丸间质细胞中睾酮产生的潜在机制，解释了 EE2 对男性生殖的损害作用。
