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Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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<jats:sub>\u03b1q<\/jats:sub> 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<jats:sub>\u03b1q<\/jats:sub> 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<jats:sub>\u03b1q<\/jats:sub> expression in these brain regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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<jats:sub>\u03b1q<\/jats:sub> 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<jats:sub>\u03b1q<\/jats:sub> protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:sub>\u03b1q<\/jats:sub> 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<jats:sub>\u03b1q<\/jats:sub> expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or G<jats:sub>\u03b1q<\/jats:sub> expression in any of the brain regions examined. AR45 expression was positively correlated with G<jats:sub>\u03b1q<\/jats:sub> expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings reveal enrichment of AR45 and G<jats:sub>\u03b1q<\/jats:sub> 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<jats:sub>\u03b1q<\/jats:sub>. Importantly, there are sex differences in AR45 expression and its association with G<jats:sub>\u03b1q<\/jats:sub> expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1420144","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T04:33:34Z","timestamp":1721277214000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of sex and hypoxia on brain region-specific expression of membrane androgen receptor AR45 in rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Jessica L.","family":"Bradshaw","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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