The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus

Bai, Guoliang; Hu, Kai-Li; Huan, Yi; Wang, Xing; Lei, Lei; Zhang, Meng; Guo, Chunyan; Chang, Hong-Sheng; Zhao, Libo; Liu, Jing; Shen, Zhufang; Wang, Xiaoling; Ni, Xin

doi:10.3389/fphar.2020.596525

Cited by 10 publications

(7 citation statements)

References 65 publications

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“…The PP rat model has been used in several previous studies to evaluate the effects of herbal mixtures from Oriental medicine. Recently, Bai et al studied the effect of the Fuyou formula, containing Anemarrhenae rhizome and Rehmanniae radix , on GT1-7 cells and danazol-induced PP rats [ 26 ]. The results showed that the Fuyou formula alleviated the symptoms in rats with PP and downregulated the GPR54/GnRH signaling pathway in GT1-7 cells.…”

Section: Discussionmentioning

confidence: 99%

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Kim

Trinh²,

Baek

et al. 2021

Plants

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Anemarrhenae rhizome and Phellodendri cortex have historically been used for the treatment of precocious puberty (PP) in oriental medicine. Our study aimed to evaluate the effect of APE, a mixture of the extracts from these herbs, against danazol-induced PP in female rats. The offspring were injected danazol to establish the PP model, and then treated with APE daily, and observed for vaginal opening. At the end of the study, the levels of gonadotropic hormones, such as estradiol, follicle-stimulating hormone, and luteinizing hormone, were determined by ELISA. Moreover, the mRNA expression of GnRH, netrin-1, and UNC5C in hypothalamic tissues was determined by real-time PCR. Network pharmacological analysis was performed to predict the active compounds of APE and their potential actions. APE treatment delayed vaginal opening in rats with PP. In addition, APE treatment reduced LH levels and suppressed UNC5C expression. Gene set enrichment analysis revealed that the targets of APE were significantly associated with GnRH signaling and ovarian steroidogenesis pathways. In conclusion, APE may be used as a therapeutic remedy to inhibit the activation of the hypothalamic–pituitary–gonadal axis.

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Section: Discussionmentioning

confidence: 99%

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Kim

Trinh²,

Baek

et al. 2021

Plants

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“…Moreover, it has been reported that the treatment with Fy formula can result in a significantly reduction in the level of E2, LH and FSH in Sprague-Dawley rats ( Guo et al, 2021b ). Furthermore, it has been illustrated that the Fy formula is able to downregulate the expression of Kiss1, GPR54, and GnRH in female rats ( Bai et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has been showed that the Fy formula induces downregulation of the mRNA expression of kiss1, GPR54, and GnRH in female rats ( Bai et al, 2020 ). A previous integrated pharmacological study on the mechanism of Fy formula in treating PP demonstrated that it can effectively reduce the levels of FSH, LH, and E 2 in Sprague-Dawley rats ( Guo et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty

et al. 2022

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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.

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“…Studies have reported that GnRH release may be related to PKC and phosphorylated ERK1/2, as phosphorylation of these proteins is considered the main cellar signaling event in the activation of the GPR54-GnRH pathway (32,33). To further explore the potential molecular regulatory mechanism of gut microbiota-derived SCFAs of the GPR54-GnRH signaling pathway in the hypothalamus, we measured the protein levels of GPR54, PKC, and ERK1/2 in the hypothalamus (Figure 8A) and examined the secretion of GnRH in the hypothalamus between the HF group and the SCFAs supplement groups.…”

Section: Scfas Regulate Hypothalamic Gnrh Release Through the Gpr54-p...mentioning

confidence: 99%

Gut microbiota and its derived SCFAs regulate the HPGA to reverse obesity-induced precocious puberty in female rats

Wang

Tan

et al. 2022

Front. Endocrinol.

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The intestinal microbiota and its derived short-chain fatty acids (SCFAs) can reverse obesity and obesity-related metabolic diseases, but whether it has an effect on obesity complicated by precocious puberty and its potential mechanism need to be further understood. The purpose of this study was to investigate the effect of the gut microbiota and its derived short-chain fatty acids (SCFAs) on obesity-induced precocious puberty rats and their regulatory mechanisms. We constructed obesity-induced precocious puberty rats using a high-fat diet (HFD) had notable similarity to precocious puberty caused by obesity due to overeating in children. We then added acetate, propionate, butyrate or their mixture to the HFD, and investigated the effect of intestinal microbiota and its derived SCFAs on the hypothalamic-pituitary-gonadal axis (HPGA) in rats with obesity-induced precocious puberty. We found that obesity-induced precocious puberty rats had an early first estrous cycle, increased hypothalamic mRNA expression of Kiss1, GPR54 and GnRH, and early gonadal maturation. Meanwhile, the intestinal microbiota imbalance and the main SCFAs production decreased in the colon. The addition of acetate, propionate, butyrate or their mixture to the HFD could significantly reverse the precocious puberty of rats, reduce GnRH release from the hypothalamus and delay the development of the gonadal axis through the Kiss1–GPR54–PKC–ERK1/2 pathway. Our findings suggest that gut microbiota-derived SCFAs are promising therapeutic means for the prevention of obesity-induced precocious puberty and provide new therapeutic strategies with clinical value.

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The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus

Cited by 10 publications

References 65 publications

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty

Gut microbiota and its derived SCFAs regulate the HPGA to reverse obesity-induced precocious puberty in female rats

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