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雄激素受体基因敲除雌性小鼠低剂量 DHT 处理后的生殖表现

Reproductive Profile of Neuronal Androgen Receptor Knockout Female Mice With a Low Dose of DHT.

机构信息

Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA.

Department of Cellular and Molecular Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

出版信息

Endocrinology. 2024 Jan 16;165(3). doi: 10.1210/endocr/bqad199.

Abstract

Hyperandrogenism and polycystic ovarian syndrome result from the imbalance or increase of androgen levels in females. Androgen receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron-specific AR knockout (KO) mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone, and estradiol were comparable between the control and the SynARKO mice. There were no differences in cyclicity and fertility between the control and SynARKO mice, with similar impairment in both groups on DHT treatment. Neuronal AR KO, as in this SynARKO mouse model, did not alleviate the infertility associated with DHT treatment. These studies suggest that neuronal AR KO neither altered reproductive function under physiological androgen levels, nor restored fertility under hyperandrogenic conditions.

摘要

高雄激素血症和多囊卵巢综合征是由于女性体内雄激素水平失衡或升高所致。雄激素受体(AR)介导雄激素的作用,本研究探讨了在正常和雄激素升高的情况下,神经元 AR 是否在雌性小鼠的生殖中发挥作用。神经元特异性 AR 敲除(KO)小鼠(SynARKO)由雌性小鼠(突触素启动子驱动 Cre)和雄性小鼠(Ar fl/y)产生。对照组和 SynARKO 小鼠的性成熟和生殖激素水平(如 LH、FSH、睾酮和雌二醇)相当。对照组和 SynARKO 小鼠的周期性和生育能力没有差异,两组在 DHT 治疗后都有类似的损伤。神经元 AR KO,如在这种 SynARKO 小鼠模型中,并没有减轻与 DHT 治疗相关的不孕。这些研究表明,神经元 AR KO 既没有改变生理雄激素水平下的生殖功能,也没有在高雄激素条件下恢复生育能力。

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