Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
J Steroid Biochem Mol Biol. 2020 Nov;204:105752. doi: 10.1016/j.jsbmb.2020.105752. Epub 2020 Sep 28.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in women with polycystic ovarian syndrome (PCOS) than that in healthy women. This association can be explained in part by the resistance to insulin and the prevalence of obesity, which are fueled by high androgen levels. However, there is little evidence of the involvement of endogenous testosterone in hepatic steatosis in women with PCOS. Here, we treated Sprague Dawley rats with the aromatase inhibitor, letrozole, to increase the endogenous testosterone level and to decrease the estradiol levels. We also quantified the testosterone levels in human serum specimens and HepG2 cells to investigate the effects of androgens on hepatic steatosis and liver dysfunction.
Twenty-nine PCOS patients and twenty healthy women were enrolled. Alanine transaminase and aspartate transaminase (AST) levels were increased in women with PCOS, and a strong correlation between testosterone and AST levels was observed. After letrozole treatment for 90 days, rats were significantly more obese, with animals developing hepatic steatosis and moderate insulin resistance. Additional experiments revealed that excess androgen inhibited the AMP-activated protein kinase alpha pathway in letrozole-treated livers and dihydrotestosterone (DHT)-treated HepG2 cells, thereby causing steatosis.
Our results show that an elevated endogenous testosterone level can induce hepatic steatosis. Decreasing the endogenous testosterone level in hepatocytes may represent a new approach in the treatment of NAFLD in PCOS patients.
多囊卵巢综合征（PCOS）女性中非酒精性脂肪性肝病（NAFLD）的患病率高于健康女性。这种相关性部分可以通过胰岛素抵抗和肥胖的流行来解释，而肥胖是由高水平的雄激素引起的。然而，关于内源性睾酮在 PCOS 女性肝脂肪变性中的作用，证据很少。在这里，我们用芳香化酶抑制剂来曲唑治疗 Sprague Dawley 大鼠，以增加内源性睾酮水平并降低雌二醇水平。我们还定量检测了人血清标本和 HepG2 细胞中的睾酮水平，以研究雄激素对肝脂肪变性和肝功能障碍的影响。
共纳入 29 名 PCOS 患者和 20 名健康女性。PCOS 患者的丙氨酸转氨酶和天冬氨酸转氨酶（AST）水平升高，且睾酮与 AST 水平呈强相关。用来曲唑治疗 90 天后，大鼠明显肥胖，出现肝脂肪变性和中度胰岛素抵抗。进一步的实验表明，过量的雄激素抑制了来曲唑处理肝脏和二氢睾酮（DHT）处理 HepG2 细胞中的 AMP 激活蛋白激酶α通路，从而导致脂肪变性。
我们的结果表明，内源性睾酮水平升高可诱导肝脂肪变性。降低肝细胞内源性睾酮水平可能代表治疗 PCOS 患者 NAFLD 的一种新方法。
