Chronic ethanol exposure alters hypothalamic expression of genes regulating the hypothalamic–pituitary–thyroid axis

Chronic alcohol consumption induces persistent neurobiological changes that contribute to cognitive and emotional disturbances. Although the hypothalamus plays a central role in neuroendocrine and emotional regulation, its molecular alterations under chronic alcohol exposure remain poorly understood. This study aimed to characterize transcriptomic changes in the hypothalamus of alcohol-exposed mice and identify the affected signaling pathways. Male mice were subjected to chronic alcohol exposure. Hypothalamic tissues were analyzed via RNA sequencing, followed by KEGG, GO, and Reactome enrichment analyses. Quantitative real-time PCR (qRT-PCR) was performed to validate selected differentially expressed genes. Transcriptomic profiling and integrative pathway analyses revealed significant differential expression of genes associated with the hypothalamic – pituitary – thyroid (HPT) axis. Notably, Dio2 and Adcy9 were downregulated, while Cga was upregulated in the hypothalamus of alcohol-exposed mice, suggesting a potential disruption in neuroendocrine feedback regulation. The altered expression of HPT axis – related genes in the hypothalamus may reflect compensatory neuroendocrine adaptations to chronic alcohol exposure. These findings offer insights into central regulatory mechanisms underlying alcohol-induced hypothalamic dysfunction and provide a basis for further mechanistic studies.