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Updated: Aug 8, 2026

Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
Published on: September 4, 2011
Stigmasterol alleviates central precocious puberty by targeting the IGF-1/PI3K/Akt/mTOR signaling pathway and
Lin Dong1, Yan Xing1, Xiaoning Li2
1Department of endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Sciences and Technology of China, Hefei City, 230001, Anhui Province, China.
Background:
Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis, causing early sexual development and related health risks. Stigmasterol (ST), a natural phytosterol with diverse pharmacological activities, has not been fully evaluated for CPP.
Methods:
This study integrated network pharmacology, molecular docking, and molecular dynamics simulations to identify ST targets in CPP. Experimental validation used an N-Methyl aspartic acid-induced CPP rat model and high-glucose high-fat-stimulated GT1-7 hypothalamic neurons. Techniques included histology, ELISA, qPCR, western blot, and flow cytometry.
Results:
In silico analyses demonstrated favorable binding of ST to core proteins within the IGF-1/PI3K/Akt/mTOR signaling pathway. In vivo, ST treatment significantly delayed vaginal opening, reduced serum levels of estradiol and testosterone, and ameliorated pathological abnormalities in uterine and ovarian tissues. At the molecular level, ST suppressed the hypothalamic overactivation of the IGF-1/PI3K/Akt/mTOR pathway and attenuated neuronal damage and apoptosis. In vitro, ST inhibited HGHF-induced proliferation, inflammatory cytokine release, and apoptosis in GT1-7 cells, while concurrently modulating the expression of key puberty-related genes and proteins, including those within the Kisspeptin/GnRH axis. Conversely, pharmacological reactivation of PI3K signaling with the agonist 740YP attenuated selected protective effects the protective effects of ST, supporting the functional involvement the PI3K/Akt/mTOR pathway in mediating these benefits.
Conclusions:
Stigmasterol exhibits significant therapeutic effects against CPP by concurrently targeting the IGF-1/PI3K/Akt/mTOR and Kisspeptin/GnRH signaling pathways. These findings provide robust preclinical evidence supporting ST as a promising multi-targeted natural candidate for CPP management.
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