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Dai, X., He, Y., Li, S., Sun, Y., Sun, W., Tian, Z., Yu, J., Ablakimova, N., & Wang, Y. (2024). Modulating the RFamide-related peptide- 3/G protein-coupled receptor 147 signaling pathway with nourishing Yin-removing fire herbal mixture to alleviate precocious puberty in female rats: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 22(1), 31–42. https://doi.org/10.18502/ijrm.v22i1.15240

https://doi.org/10.18502/ijrm.v22i1.15240

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authors

  • Xiaoli Dai

    Xiaoli Dai

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.
  • Yuanyuan He

    Yuanyuan He

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.
  • Suhuan Li

    Suhuan Li

    Yantaishan Hospital, Shangdong, China.
  • Yanyan Sun

    Yanyan Sun

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.
  • Wen Sun

    Wen Sun

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.
  • Zhanzhuang Tian

    Zhanzhuang Tian

    Department of Integrative Medicine and Neurobiology, Fudan University, Shanghai, China.
  • Jian Yu

    Jian Yu

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.
  • Nurgul Ablakimova

    Nurgul Ablakimova

    Department of Pharmacology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
  • Yonghong Wang

    Yonghong Wang

    Traditional Chinese Medicine Department, Children’s Hospital of Fudan University, Shanghai, China.

Published Date

  • Feb 18, 2024

Modulating the RFamide-related peptide- 3/G protein-coupled receptor 147 signaling pathway with nourishing Yin-removing fire herbal mixture to alleviate precocious puberty in female rats: An experimental study

International Journal of Reproductive BioMedicine (IJRM) / International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 1 / Pages 31–42

Abstract

Background: Precocious puberty (PP) involves early activation of the hypothalamic gonadotropin-releasing hormone (GnRH) generator. The RFamide-related peptide/G protein-coupled receptor 147 (RFRP3/GPR147) 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.


Objective: This study aimed to assess the impact of the NYRF herbal mixture on the RFRP3/GPR147 signaling pathway in the hypothalamus and its potential in alleviating PP in female rats.


Materials and Methods: In a controlled experiment, 24 female Sprague-Dawley rats (means ± SD weight = 11.20 ± 0.69 gr and age = 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.


Results: 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.


Conclusion: The NYRF herbal mixture delayed sexual development in rats with PP by hypothalamic upregulating RFRP3 and downregulating GnRH and kisspeptin.


Key words: Nourishing Yin-removing fire, RFamide-related peptide-3, G proteincoupled receptor 147, Hypothalamus, Puberty, Precocious. 

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