Tsai Yi-Ru, Liao Yen-Nung, Tsai Cheng-Ju, Lee Yu-Ang, Hsia Shih-Min, Lan Kuo-Chung, Kang Hong-Yo
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
An-Ten Obstetrics and Gynecology Clinic, Kaohsiung 802, Taiwan.
Biomedicines. 2025 Apr 29;13(5):1077. doi: 10.3390/biomedicines13051077.
: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. While canonical androgens like testosterone (T) and dihydrotestosterone (DHT) are well studied in PCOS pathophysiology, the role of 11-ketotestosterone (11KT) remains unclear. This study investigates the differential effects of these androgens on folliculogenesis, ovulation, and steroidogenesis using in vivo and in vitro models. : Four-week-old female C57BL/6 mice received T, DHT, or 11KT for six weeks. The assessments included body weight, estrous cyclicity, serum hormone profiles, ovarian histology, and follicle classification. In parallel, large preantral follicles were cultured with each androgen to evaluate follicle growth, antrum formation, and ovulation capacity. Androgen receptor (AR) signaling and steroidogenic function were analyzed using western blotting, RT-qPCR, and luciferase reporter assays. : The DHT-treated mice exhibited increased weight gain, whereas 11KT-treated mice showed reduced weight gain. T and DHT disrupted the estrous cycle, while 11KT prolonged diestrus. All androgen treatments led to ovarian morphological changes, including follicular arrest and cystic features. In vitro, all androgens enhanced follicle growth, but only T and DHT inhibited ovulation. The AR expression was elevated across all androgen-treated groups, but only DHT significantly activated AR and CYP19A1 promoters. : 11KT induces a distinct and milder PCOS-like phenotype compared to classical androgens, promoting follicle growth with minimal impact on ovulation or steroidogenic disruption. These findings underscore the heterogeneity of PCOS and suggest that different androgen profiles may drive diverse clinical phenotypes. By elucidating the distinct roles of different androgens, this may lead to better stratification of PCOS phenotypes based on predominant androgen types for more precise diagnosis and individualized management.
多囊卵巢综合征（PCOS）是一种常见的女性内分泌紊乱疾病，其特征为高雄激素血症、排卵功能障碍和多囊卵巢形态。虽然睾酮（T）和双氢睾酮（DHT）等经典雄激素在PCOS病理生理学中已得到充分研究，但11-酮睾酮（11KT）的作用仍不明确。本研究使用体内和体外模型研究这些雄激素对卵泡发生、排卵和类固醇生成的不同影响。
四周龄雌性C57BL/6小鼠接受T、DHT或11KT处理六周。评估内容包括体重、发情周期、血清激素谱、卵巢组织学和卵泡分类。同时，将大的窦前卵泡与每种雄激素一起培养，以评估卵泡生长、卵泡腔形成和排卵能力。使用蛋白质免疫印迹法、逆转录定量聚合酶链反应（RT-qPCR）和荧光素酶报告基因检测分析雄激素受体（AR）信号传导和类固醇生成功能。
接受DHT处理的小鼠体重增加，而接受11KT处理的小鼠体重增加减少。T和DHT扰乱发情周期，而11KT延长动情间期。所有雄激素处理均导致卵巢形态改变，包括卵泡停滞和囊性特征。在体外，所有雄激素均促进卵泡生长，但只有T和DHT抑制排卵。所有雄激素处理组的AR表达均升高，但只有DHT显著激活AR和CYP19A1启动子。
与经典雄激素相比，11KT诱导出一种独特且较轻的PCOS样表型，促进卵泡生长，对排卵或类固醇生成破坏的影响最小。这些发现强调了PCOS的异质性，并表明不同的雄激素谱可能导致不同临床表型。通过阐明不同雄激素的独特作用，这可能有助于基于主要雄激素类型对PCOS表型进行更好的分层，以实现更精确的诊断和个体化管理。
