{"doi":"10.3389/fendo.2024.1420144","title":"Impact of sex and hypoxia on brain region-specific expression of membrane androgen receptor AR45 in rats","abstract":"Background Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. Notably, oxidative stress-associated neuronal cell death can be exacerbated through testosterone signaling via membrane androgen receptor AR45, which is complexed with G protein G αq within plasma membrane-associated lipid rafts. The objective of this study was to elucidate the impact of sex on the expression of AR45 and G αq in brain regions associated with cognitive function, specifically hippocampus subregions and entorhinal cortex. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and G αq expression in these brain regions. Methods Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia (room air) during their sleep phase for 14 days. We quantified AR45 and G αq protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, dentate gyrus (DG), and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and G αq protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)]. Results The highest AR45 levels were expressed in the hippocampal CA1 and DG while the lowest expression was observed in the extrahippocampal STR. The highest G αq levels were expressed in the hippocampal-associated ETC while the lowest expression was observed in the extrahippocampal TH. Females expressed higher levels of AR45 in the hippocampal DG compared to males, while no sex differences in G αq expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or G αq expression in any of the brain regions examined. AR45 expression was positively correlated with G αq expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner. Conclusion Our findings reveal enrichment of AR45 and G αq protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Nonetheless, CIH does not modulate the expression of AR45 or G αq . Importantly, there are sex differences in AR45 expression and its association with G αq expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.","journal":"Frontiers in Endocrinology","year":2024,"id":456211,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":636054,"name":"E. Nicole Wilson","orcid":"0000-0001-6119-7597","position":1,"is_corresponding":false},{"id":636052,"name":"Steve Mabry","orcid":"0000-0003-0719-8059","position":2,"is_corresponding":false},{"id":1280638,"name":"Pawan Shrestha","orcid":"0000-0002-2808-7043","position":3,"is_corresponding":false},{"id":890251,"name":"Jennifer J. Gardner","orcid":"0000-0003-3784-9190","position":4,"is_corresponding":false},{"id":308571,"name":"Rebecca L. Cunningham","orcid":"0000-0001-5984-5516","position":5,"is_corresponding":false},{"id":400643,"name":"Jessica L. Bradshaw","orcid":"0000-0003-4011-8401","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:03:27.785212Z","pmid":"39092288","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}