Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Phytomedicine. 2024 Oct;133:155931. doi: 10.1016/j.phymed.2024.155931. Epub 2024 Aug 7.
Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders. Accumulated evidence has suggested the indispensable role of kisspeptin-G protein-coupled receptor (GPR54) system and SHBG in development of PCOS. However, potential mechanisms and their relationship are unclear. Jiawei Buzhong Yiqi Decoction (JWBZYQ) has been reported to ameliorate obese PCOS. Whereas, potential mechanisms remain elusive.
To determine whether JWBZYQ attenuates PCOS by regulating the kisspeptin-GPR54 system and SHBG production. And to explore potential mechanisms.
An overweight PCOS rat model was developed with testosterone propionate (TP) and high-fat diet (HFD). The efficacy of JWBZYQ was assessed by tracking changes in weight, estrous cycle, ovarian morphology, and serum sex hormone levels. Additionally, kisspeptin-GPR54 system expression in multiple organs and PI3K-AKT pathway activity in liver of different rats were detected. Modifications in SHBG production were also measured. Kisspeptin54 was administered to establish a cellular model. The levels of AKT phosphorylation and SHBG protein within HepG2 cells were analyzed. Finally, confirmatory studies were performed using AKT phosphorylation activator and inhibitor.
JWBZYQ effectively attenuated the overweight, disrupted estrous cycle, altered sex hormone levels, and aberrant ovarian morphology in PCOS rats. Meanwhile, PCOS rats exhibited elevated levels of kisspeptin and GPR54, along with reduced SHBG levels, which could be reversed by JWBZYQ. These alterations might be connected with the activation of AKT phosphorylation. In vitro experiment identified that JWBZYQ could rectify the hyperactivated AKT phosphorylation and deficient production of SHBG caused by kisspeptin54.
Overexpressed kisspeptin-GPR54 system inhibited SHBG synthesis in PCOS. JWBZYQ curtailed the exorbitant expression of kisspeptin and GPR54, which moderated the rise in AKT phosphorylation and subsequently promoted the production of SHBG.
多囊卵巢综合征（PCOS）是最常见的生殖内分泌疾病之一。越来越多的证据表明，kisspeptin-G 蛋白偶联受体（GPR54）系统和 SHBG 在 PCOS 的发生发展中起着不可或缺的作用。然而，其潜在的机制及其关系尚不清楚。加味补中益气汤（JWBZYQ）已被报道可改善肥胖型 PCOS，但潜在机制仍不清楚。
确定 JWBZYQ 是否通过调节 kisspeptin-GPR54 系统和 SHBG 产生来减轻 PCOS，并探讨潜在的机制。
用丙酸睾酮（TP）和高脂饮食（HFD）建立超重 PCOS 大鼠模型。通过跟踪体重、发情周期、卵巢形态和血清性激素水平的变化来评估 JWBZYQ 的疗效。此外，还检测了不同大鼠多个器官中的 kisspeptin-GPR54 系统表达和肝脏中的 PI3K-AKT 通路活性，并测量了 SHBG 产生的变化。给予 kisspeptin54 建立细胞模型，分析 HepG2 细胞内 AKT 磷酸化和 SHBG 蛋白的水平。最后，使用 AKT 磷酸化激活剂和抑制剂进行了验证性研究。
JWBZYQ 能有效减轻 PCOS 大鼠的超重、发情周期紊乱、性激素水平改变和卵巢形态异常。同时，PCOS 大鼠的 kisspeptin 和 GPR54 水平升高，SHBG 水平降低，而 JWBZYQ 可逆转这些变化。这些变化可能与 AKT 磷酸化的激活有关。体外实验表明，JWBZYQ 可纠正 kisspeptin54 引起的 AKT 磷酸化过度激活和 SHBG 产生不足。
过表达的 kisspeptin-GPR54 系统抑制了 PCOS 中 SHBG 的合成。JWBZYQ 降低了 kisspeptin 和 GPR54 的过度表达，从而降低了 AKT 磷酸化的升高，并随后促进了 SHBG 的产生。
