biostudies-literatureLi LNational High Level Hospital Clinical Research FundingNational Natural Science Foundation of ChinaRP100346https://www.ebi.ac.uk/biostudies/studies/S-EPMC12463393biostudies-literatureUnknown13This study investigated 17α-estradiol's effects on aged hypothalamic physiological activity via long-term administration. Single-nucleus transcriptomic sequencing (snRNA-seq) was performed on pooled hypothalami from each group: aged male Norway brown rats treated with 17α-estradiol (O.T), aged controls (O), and young controls (Y). Supervised clustering of neurons (based on neuropeptides/receptors) evaluated subtype responses to aging and 17α-estradiol. Aging-induced elevation of neuronal cellular metabolism, stress, and reduced synapse formation-related pathways were significantly attenuated by 17α-estradiol. Neuron population analysis showed that subtypes regulating food intake, reproduction, blood pressure, stress response, and electrolyte balance were sensitive to 17α-estradiol. 17α-esteLifeThe effects of 17α-estradiol treatment on endocrine system revealed by single-nucleus transcriptomic sequencing of hypothalamus.PMC12463393821716212022-PUMCH-A-2318217256631271448Yang JYang ZShan YLi YXing LYi LMo ZWu GXu XYu ZLi LfalseThe effects of 17α-estradiol treatment on endocrine system revealed by single-nucleus transcriptomic sequencing of hypothalamus.This study investigated 17α-estradiol's effects on aged hypothalamic physiological activity via long-term administration. Single-nucleus transcriptomic sequencing (snRNA-seq) was performed on pooled hypothalami from each group: aged male Norway brown rats treated with 17α-estradiol (O.T), aged controls (O), and young controls (Y). Supervised clustering of neurons (based on neuropeptides/receptors) evaluated subtype responses to aging and 17α-estradiol. Aging-induced elevation of neuronal cellular metabolism, stress, and reduced synapse formation-related pathways were significantly attenuated by 17α-estradiol. Neuron population analysis showed that subtypes regulating food intake, reproduction, blood pressure, stress response, and electrolyte balance were sensitive to 17α-estradiol. 17α-est2025-01-01T00:00:00Z2025 Sep2026-06-03T20:29:26.142Z2026-06-01T03:06:32.321ZS-EPMC124633934099680910.7554/eLife.100346