Zhang Yi, Sun Ning, Zhang Meng, Ding Qian, Wang Qian, Liang Yuguang, He Huan, Yang Yuxin, Guo Chunyan
Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Pharmacol. 2022 Mar 11;13:852550. doi: 10.3389/fphar.2022.852550. eCollection 2022.
The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.
复幼（Fy）方是一种院内制剂，由中药组成，已用于治疗性早熟（PP）20多年。在本研究中，我们旨在阐明Fy方及其主要成分对性早熟的作用。为了证实Fy方对下丘脑促性腺激素释放激素（GnRH）释放的影响，用雌激素处理GT1-7细胞建立模型组，随后用Fy方及其主要成分处理，以探讨它们对GnRH分泌的影响。采用酶联免疫吸附测定法测定GT1-7细胞中GnRH的水平。结果表明，与模型组相比，Fy方抑制了GnRH的释放。此外，通过实时聚合酶链反应（RT-qPCR）检测与GnRH分泌相关的蛋白质的表达水平，包括GnRH、促性腺激素释放激素受体（GnRHR）、Kiss-1转移抑制因子（Kiss1）、G蛋白偶联受体54（GPR54）、雌激素受体α（ERα）、胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子-1受体（IGF-1R）。结果表明，与模型组相比，Fy方显著降低了GT1-7细胞系中GnRH的分泌水平。此外，它还显著下调了GnRH、GnRHR、Kiss1、GPR54、ERα、IGF-1和IGF-1R的表达。总之，我们的结果表明，Fy方及其主要成分可能抑制雌激素的作用，通过对靶基因的转录调控来缓解性早熟。
