Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Pediatrics, Seattle's Children's Hospital, University of Washington, Seattle, WA, United States.
Front Endocrinol (Lausanne). 2022 Jun 9;13:868572. doi: 10.3389/fendo.2022.868572. eCollection 2022.
Obesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity in female mice, and conditional knock-out of the androgen receptor (Ar) in the liver (LivARKO) protects female mice from DHT-induced glucose intolerance and hyperinsulinemia. Since altered metabolic function will regulate reproduction, and liver plays a pivotal role in the reversible regulation of reproductive function, we sought to determine the reproductive phenotype of LivARKO mice under normal and hyperandrogenemic conditions. Using Cre/Lox technology, we deleted the in the liver, and we observed LivARKO female mice have normal puberty timing, cyclicity and reproductive function. After DHT treatment, like control mice, LivARKO experience altered estrous cycling, reduced numbers of corpus lutea, and infertility. Liver Ar is not involved in hyperandrogenemia-induced reproductive dysfunction. The reproductive dysfunction in the DHT-treated LivARKO lean females with normal glucose homeostasis indicates that androgen-induced reproductive dysfunction is independent from metabolic dysfunction.
肥胖、葡萄糖稳态改变、高胰岛素血症和生殖功能障碍在患有高雄激素血症的女性和哺乳动物中发展。我们之前报道过，低剂量二氢睾酮（DHT）给药会导致雌性小鼠代谢和生殖功能障碍，而肝脏中雄激素受体（Ar）的条件敲除（LivARKO）可保护雌性小鼠免受 DHT 引起的葡萄糖不耐受和高胰岛素血症的影响。由于代谢功能的改变会调节生殖功能，而肝脏在生殖功能的可逆调节中起着关键作用，因此我们试图确定 LivARKO 小鼠在正常和高雄激素血症条件下的生殖表型。使用 Cre/Lox 技术，我们在肝脏中删除了 ，我们观察到 LivARKO 雌性小鼠具有正常的青春期时间、周期性和生殖功能。在 DHT 治疗后，与对照组小鼠一样，LivARKO 经历了发情周期改变、黄体数量减少和不孕。肝脏中的 Ar 不参与高雄激素血症引起的生殖功能障碍。DHT 处理的 LivARKO 瘦型雌性小鼠具有正常葡萄糖稳态，但仍存在生殖功能障碍，表明雄激素引起的生殖功能障碍与代谢功能障碍无关。
