Modulating the RFamide-related peptide-۳/G protein-coupled receptor ۱۴۷ signaling pathway with nourishing Yin-removing fire herbal mixture to alleviate precocious puberty in female rats: An experimental study

Background: Precocious puberty (PP) involves early activation of the hypothalamic gonadotropin-releasing hormone (GnRH) generator. The RFamide-related peptide/G protein-coupled receptor ۱۴۷ (RFRP۳/GPR۱۴۷) 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 RFRP۳/GPR۱۴۷ signaling pathway in the hypothalamus and its potential in alleviating PP in female rats. Materials and Methods: In a controlled experiment, ۲۴ female Sprague-Dawley rats (۱۱.۲۰ ± ۰.۶۹ gr, postnatal day [PD۵]) were divided into normal, model, normal saline, and NYRF groups (n = ۶/each). PP was induced in the model, normal saline, and NYRF groups by subcutaneous injection of danazol at PD۵. The NYRF herbal mixture or normal saline was administered from PD۱۵. Serum sex hormone levels and hypothalamic samples were collected for mRNA and protein expression at PD۳۰. Results: In the model group, hypothalamic GnRH and kisspeptin levels increased, while RFRP۳ and GPR۱۴۷ 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 RFRP۳ 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 RFRP۳ and downregulating GnRH and kisspeptin.

Keywords:

Nourishing Yin-removing fire , RFamide-related peptide-۳ , G protein-coupled receptor ۱۴۷ , Hypo-thalamus , Puberty , Precocious. , مخلوط گیاهی Yin-removing fire , پپتید-۳ مرتبط با RFamide , گیرنده ۱۴۷ متصل به پروتئین G , هیپوتالاموس , بلوغ , زودرس.