Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
J Ovarian Res. 2023 Jan 17;16(1):15. doi: 10.1186/s13048-022-01078-x.
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Electroacupuncture (EA) can effectively improve hyperandrogenism and increase ovulation frequency in patients with PCOS. Pieces of suggest that androgen activity in the brain is associated with impaired steroid negative feedback in such patients. Studies have shown that EA regulated androgen receptor (AR) expression and local factor levels (such as anti-Müllerian hormone and inhibin B) in the ovary of PCOS rats. However, few studies have explored the effect of EA on androgen activity in the brain.
This study investigated the effect of EA on the kisspeptin-gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) neural circuit and sex hormone receptor expression in the hypothalamus of PCOS rats.
PCOS signs were induced by letrozole administration, and the induced rats were treated with low-frequency EA at Guan Yuan acupoint (CV4). The effect of EA on PCOS-like signs was evaluated by observing changes in the body weight, ovarian quality, ovarian morphology, and serum sex hormone levels in rats. To explore the mechanism of the effect of EA on PCOS-like signs, the neuropeptide content of the kisspeptin-GnRH/LH neural circuit was assessed using enzyme-linked immunosorbent assay(ELISA); AR and estrogen receptor α (ERα) coexpression on kisspeptin/neurokinin B/dynorphin (KNDy) neurons was determined via triple-label immunofluorescence; and protein and mRNA expression of Kiss1, Ar, Esr1, and kisspeptin receptor (Kiss1r) was evaluated via western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR).
The results revealed that the estrous cycle of rats in the EA treatment group recovered, and their body and ovary weight reduced; ovarian morphology improved; serum testosterone and LH levels significantly decreased; and kisspeptin, GnRH, and dynorphin levels in hypothalamic arcuate nucleus significantly decreased. Compared with controls, the number of AR/Kiss1-positive cells increased, number of ERα/Kiss1-positive cells decreased, and protein and mRNA expression of Kiss1, Ar, and Kiss1r significantly increased in PCOS rats. However, EA treatment reversed these changes and reduced the expression of Kiss1, Ar, and Kiss1r significantly.
Improvement in the reproductive hallmarks of PCOS rats via EA may be achieved by regulating the kisspeptin-GnRH/LH circuit via androgen activity attenuation. Thus, the results provide an experimental basis for acupuncture as an adjuvant medical therapy on PCOS.
多囊卵巢综合征（PCOS）的特征是高雄激素血症、排卵障碍和多囊卵巢。电针（EA）可以有效改善 PCOS 患者的高雄激素血症和增加排卵频率。有研究表明，此类患者的大脑中的雄激素活性与类固醇负反馈受损有关。研究表明，EA 调节了 PCOS 大鼠卵巢中的雄激素受体（AR）表达和局部因子水平（如抗苗勒管激素和抑制素 B）。然而，很少有研究探讨 EA 对大脑中雄激素活性的影响。
本研究旨在探讨 EA 对 PCOS 大鼠 kisspeptin-促性腺激素释放激素（GnRH）/黄体生成素（LH）神经回路和下丘脑性激素受体表达的影响。
采用来曲唑给药诱导 PCOS 征象，并用低频 EA 处理关元穴（CV4）。通过观察大鼠体重、卵巢质量、卵巢形态和血清性激素水平的变化来评价 EA 对 PCOS 样征象的影响。为了探讨 EA 对 PCOS 样征象影响的机制，采用酶联免疫吸附试验（ELISA）评估 kisspeptin-GnRH/LH 神经回路的神经肽含量；通过三重免疫荧光确定 kisspeptin/神经激肽 B/强啡肽（KNDy）神经元上的 AR 和雌激素受体 α（ERα）共表达；通过 Western 印迹和逆转录聚合酶链反应（RT-PCR）评估 Kiss1、Ar、Esr1 和 kisspeptin 受体（Kiss1r）的蛋白和 mRNA 表达。
结果显示，EA 治疗组大鼠的动情周期恢复，体重和卵巢重量减轻，卵巢形态改善，血清睾酮和 LH 水平显著降低，下丘脑弓状核中的 kisspeptin、GnRH 和 dynorphin 水平显著降低。与对照组相比，PCOS 大鼠的 AR/Kiss1 阳性细胞数量增加，ERα/Kiss1 阳性细胞数量减少，Kiss1、Ar 和 Kiss1r 的蛋白和 mRNA 表达显著增加。然而，EA 治疗逆转了这些变化，并显著降低了 Kiss1、Ar 和 Kiss1r 的表达。
EA 通过降低雄激素活性来调节 kisspeptin-GnRH/LH 回路，从而改善 PCOS 大鼠的生殖特征。因此，该结果为针刺作为 PCOS 的辅助治疗提供了实验依据。
