背景: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,潜在的机制及其关系尚不清楚。已报道加味补中益气汤(JWBZYQ)可改善肥胖的PCOS。然而,潜在的机制仍然难以捉摸。
目的:确定JWBZYQ是否通过调节kisspeptin-GPR54系统和SHBG产生来减弱PCOS。并探索潜在的机制。
方法:采用丙酸睾酮(TP)和高脂饮食(HFD)建立超重PCOS大鼠模型。通过跟踪体重变化来评估JWBZYQ的疗效,发情周期,卵巢形态学,和血清性激素水平.此外,检测不同大鼠肝脏组织中kisspeptin-GPR54系统的表达和PI3K-AKT通路的活性。还测量了SHBG生产中的修饰。施用Kisspeptin54以建立细胞模型。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验证性研究.
结果:JWBZYQ有效减轻了超重,动情周期中断,性激素水平改变,PCOS大鼠卵巢形态异常。同时,PCOS大鼠的kisspeptin和GPR54水平升高,同时SHBG水平降低,这可以被JWBZYQ逆转。这些改变可能与AKT磷酸化的激活有关。体外实验确定JWBZYQ可以纠正由kisspeptin54引起的过度活化的AKT磷酸化和SHBG产生不足。
结论:过表达的kisspeptin-GPR54系统抑制了PCOS中SHBG的合成。JWBZYQ减少了kisspeptin和GPR54的过度表达,从而缓和了AKT磷酸化的上升,随后促进了SHBG的产生。
BACKGROUND: 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.
OBJECTIVE: To determine whether JWBZYQ attenuates PCOS by regulating the kisspeptin-GPR54 system and SHBG production. And to explore potential mechanisms.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.