Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways

Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways

Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol...

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Main Authors: Asim Muhammad, Mubashir Muhammad, Xiaohuan Chao, Chunlei Zhang, Jiahao Chen, Huan Yang, Shuhan Liu, Yuan Ding, Ziming Wang, Hongwei Bi, Wen Guo, Junhong Fan, Bo Zhou
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Animals
Subjects:
ovariectomy
estradiol intervention
hypothalamic transcriptomics
GnRH signaling pathway
calcium signaling pathway
reproductive aging
Online Access:https://www.mdpi.com/2076-2615/15/10/1467
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Summary:Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J mice. RNA sequencing was performed to identify differentially expressed genes (DEGs) across control (CK), E2, OVX, and OVX+E2 groups, followed by functional enrichment and pathway analyses. Behavioral assessments, including open field, Y-maze, and elevated plus maze tests, were conducted to evaluate anxiety-like and cognitive behaviors. Results revealed significant alterations in GnRH signaling, neurotransmission, and inflammatory pathways, with key genes such as <i>Elk1</i>, <i>Prkcb</i>, and <i>Camk2a</i> differentially expressed in response to estrogen modulation. OVX-induced neuroendocrine disruptions were partially reversed by E2 treatment, as evidenced by transcriptomic and behavioral outcomes. Pearson correlation analysis further linked gene expression patterns with phenotypic traits, providing insights into estrogen’s regulatory mechanisms in the hypothalamus. These findings enhance our understanding of estrogen-mediated neuroendocrine regulation and may have implications for hormone replacement therapies in postmenopausal disorders.
ISSN:2076-2615

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