Dai Xiaoli, He Yuanyuan, Li Suhuan, Sun Yanyan, Sun Wen, Tian Zhanzhuang, Yu Jian, Ablakimova Nurgul, Wang Yonghong
Traditional Chinese Medicine Department, Children's Hospital of Fudan University, Shanghai, China.
Yantaishan Hospital, Shangdong, China.
Int J Reprod Biomed. 2024 Feb 23;22(1):31-42. doi: 10.18502/ijrm.v22i1.15240. eCollection 2024 Jan.
Precocious puberty (PP) involves early activation of the hypothalamic gonadotropin-releasing hormone (GnRH) generator. The RFamide-related peptide/G protein-coupled receptor 147 () signaling pathway is vital in inhibiting GnRH and delaying puberty onset. The nourishing Yin-removing fire (NYRF) herbal mixture has shown promising results in treating PP.
This study aimed to assess the impact of the NYRF herbal mixture on the signaling pathway in the hypothalamus and its potential in alleviating PP in female rats.
In a controlled experiment, 24 female Sprague-Dawley rats (11.20 0.69 gr, postnatal day [PD5]) were divided into normal, model, normal saline, and NYRF groups (n = 6/each). PP was induced in the model, normal saline, and NYRF groups by subcutaneous injection of danazol at PD5. The NYRF herbal mixture or normal saline was administered from PD15. Serum sex hormone levels and hypothalamic samples were collected for mRNA and protein expression at PD30.
In the model group, hypothalamic GnRH and kisspeptin levels increased, while RFRP3 and GPR147 levels decreased, luteinizing hormone levels elevated, reproductive organ coefficients increased, and the vagina opened earlier compared to the normal group. Conversely, the NYRF group exhibited lower GnRH and kisspeptin levels but higher RFRP3 levels in the hypothalamus. Serum luteinizing hormone levels were reduced, reproductive organ coefficients were reduced, and the vaginal opening was delayed compared to the model and normal saline groups.
The NYRF herbal mixture delayed sexual development in rats with PP by hypothalamic upregulating RFRP3 and downregulating GnRH and kisspeptin.
性早熟（PP）涉及下丘脑促性腺激素释放激素（GnRH）发生器的早期激活。RF酰胺相关肽/G蛋白偶联受体147（）信号通路在抑制GnRH和延迟青春期开始方面至关重要。滋阴泻火（NYRF）草药合剂在治疗PP方面已显示出有前景的结果。
本研究旨在评估NYRF草药合剂对下丘脑信号通路的影响及其在减轻雌性大鼠PP方面的潜力。
在一项对照实验中，将24只雌性Sprague-Dawley大鼠（11.20±0.69克，出生后第[PD5]天）分为正常组、模型组、生理盐水组和NYRF组（每组n = 6）。在出生后第5天通过皮下注射达那唑在模型组、生理盐水组和NYRF组诱导性早熟。从出生后第15天开始给予NYRF草药合剂或生理盐水。在出生后第30天收集血清性激素水平和下丘脑样本用于mRNA和蛋白质表达分析。
与正常组相比，模型组下丘脑GnRH和亲吻素水平升高，而RFRP3和GPR147水平降低，黄体生成素水平升高，生殖器官系数增加，阴道开口提前。相反，NYRF组下丘脑GnRH和亲吻素水平较低，但RFRP3水平较高。与模型组和生理盐水组相比，血清黄体生成素水平降低，生殖器官系数降低，阴道开口延迟。
NYRF草药合剂通过下丘脑上调RFRP3并下调GnRH和亲吻素，延缓了性早熟大鼠的性发育。
