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

Guo-Liang Bai,Xin Ni,Jing Liu,Kai-Li Hu,Xiao-Ling Wang,Lei Lei,Yi Huan,Hong-Sheng Chang,Xing Wang,Zhu-Fang Shen,Li-Bo Zhao,Chun-Yan Guo,Meng Zhang

doi:10.3389/fphar.2020.596525

Abstract

The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.

Highlights

Precocious puberty (PP) is one of the most common endocrine diseases in children
This study showed that subcutaneous injection of 300 μg of danazol into PND5 female rats accelerated the onset of sexual development, increased the weights of the uterus and ovary, increased the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and accelerated HPG
To confirm the effect of the Fy formula on the GPR54/GnRH signaling pathway in GT1-7 cells, we investigated its effects on related proteins and found that the Fy formula significantly downregulated the protein expression of GPR54, protein kinase C (PKC) and GnRH and the phosphorylation of Erk1/2 (Figure 5)

Summary

Introduction

Precocious puberty (PP) is one of the most common endocrine diseases in children. PP is commonly defined as puberty that starts before age eight in Chinese girls and age nine in Chinese boys (Bradley et al, 2020), before age 7.5 in African-American and Hispanic girls, and before age eight in Caucasian girls (Herman-Giddens, 2006). The male to female ratio of patients with PP is approximately 1:5–10 (Teilmann et al, 2005; Dong et al, 2020), and 74% of the cases in girls with CPP are idiopathic (Bradley et al, 2020; Tao et al, 2020). The incidence of PP in boys is low, the disorder may be caused by certain serious diseases and should be given attention (Kaplowitz and Bloch, 2016). The timing of PP onset depends on genetic and environmental factors, and numerous studies worldwide have shown that the onset of pubertal characteristics varies with race and ethnicity, genetics, environmental conditions, exposure to certain chemicals, geographical location and nutrition (Herman-Giddens et al, 2001; Latronico et al, 2016; Abbasi, 2019). Concerns about PP in girls are extremely common and are frequently raised by parents and other guardians

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