ArticleScience advances2025
Prefrontal 5α-reductase 2 mediates male-specific acute stress response.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
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Who cites it
6 citing papers in PubMed.
- Acute alcohol triggers rank-specific social ascent through a prefrontal-accumbens circuit in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Steroid 5α-reductases in the brain: From neurosteroidogenesis to therapeutic implications.Frontiers in neuroendocrinology · 2026Review
- Advances in time-sensitive assessment and intervention for acute stress reaction.Frontiers in psychology · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Counterbalancing O-GlcNAcylation and STAT3 Phosphorylation in Ventral Tegmental Area Dopaminergic Neurons Mediates Behavioral Adaptations to Acute Restraint Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuroactive steroids and the pathophysiology of PTSD: Biomarkers for treatment targeting.Neuroscience and biobehavioral reviews · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
A key response to acute stress is the increased brain synthesis of the neurosteroid allopregnanolone (AP). Although the rate-limiting step of this reaction is catalyzed by 5α-reductase (5αR), the role of its two primary isoenzymes, 5αR1 and 5αR2, in stress reactivity remains unclear. Here, we found that acute stress led to increased levels of 5αR2, but not 5αR1, in the medial prefrontal cortex (mPFC) of male, but not female, rats. Down-regulation of 5αR2 in the mPFC significantly reduced stress response in males, and similar sexual dimorphic effects were observed in a novel line of 5αR2 knockout rats. Notably, 5αR1 regulated baseline AP synthesis, whereas 5αR2 enabled AP production under stress. Acute AP administration restored stress response in 5αR2 knockdown rats. Single-nucleus transcriptomics showed that 5αR2 enabled stress-induced protein translation in neurons and glia. These results highlight the crucial role of 5αR2 in mediating sex-specific differences in acute stress reactivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.