Unveiling proteomic targets in the hypothalamus of ovariectomized and estradiol-treated rats: Insights into menopausal syndrome mechanisms

Abstract

Background

Menopausal syndrome profoundly affects the physical and mental health of many women, drawing increasing attention from the medical community. However, its pathogenesis remains unclear. These symptoms are primarily driven by hormonal fluctuation. The hypothalamus, a key regulator of hormonal balance, potentially playing a critical role in the manifestation of menopausal syndrome.

Methods

We simulated the low-estrogen menopausal state using ovariectomized rats, confirmed the success of ovariectomy via histological analysis of the uterus and vagina, followed by estrogen treatment. TMT-labeled quantitative proteomics, RTqPCR, targeted proteomics and Western blotting were used to identify differentially expressed proteins and their functions in the hypothalamus under low-estrogen conditions.

Results

One-way ANOVA (p < 0.05) identified 295 differentially expressed proteins across the sham, ovariectomized and estrogen-treated groups. Post-ovariectomy, 103 differentially expressed proteins were upregulated and 93 were downregulated. Among these, 50 proteins were involved in hormones and neurotransmitters, immunity, metabolism and cardiovascular function. Notably, four proteins—Prkcg, Hsp90ab1, Ywhae, and Gad2—were identified as crucial regulators.

Conclusions

This study elucidates the central molecular mechanism of menopausal syndrome through bioinformatics analysis of differentially expressed proteins in the hypothalamus under low-estrogen conditions, providing novel targets for the treatment of related symptoms.