ArticleProceedings of the National Academy of Sciences of the United States of America2001
Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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122 citing papers in PubMed, 261 citations in OpenAlex.
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- Levels of neuroactive steroids are elevated in those who develop first-onset depression early in pregnancy.Frontiers in psychiatry · 2025Article
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis.Journal of neuroendocrinology · 2024Article
- Developmental and adult stress: effects of steroids and neurosteroids.Stress (Amsterdam, Netherlands) · 2024Review
- Neurosteroids: mechanistic considerations and clinical prospects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Neurosteroid influence on affective tone.Neuroscience and biobehavioral reviews · 2023Review
- Biomass smoke inhalation promotes neuroinflammatory and metabolomic temporal changes in the hippocampus of female mice.Journal of neuroinflammation · 2023Article
- Impaired Endogenous Neurosteroid Signaling Contributes to Behavioral Deficits Associated With Chronic Stress.Biological psychiatry · 2023Article
- Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder.Translational psychiatry · 2023Review
- Neuroinflammatory and Metabolomic Temporal Dynamics Following Wood Smoke Inhalation.Research square · 2023Article
- Trajectories of Allopregnanolone and Allopregnanolone to Progesterone Ratio across the Six Subphases of Menstrual Cycle.Biomolecules · 2023Article
- Hippocampus-based behavioral, structural, and molecular dynamics across the estrous cycle.Journal of neuroendocrinology · 2023Review
- Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system.Cell and tissue research · 2023Review
- The role of flumazenil in generalised anxiety disorder: a pilot naturalistic open-label study with a focus on treatment resistance.Therapeutic advances in psychopharmacology · 2023Article
62 more citing papers are in PubMed but not listed here.
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9 authors at 1 institution in 1 country.
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Abstract
Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively modulates the action of GABA at these receptors. Unlike ALLO, 5alpha-dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular progesterone receptors that regulate DNA transcription. To investigate the physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted a mouse model involving protracted social isolation. In the frontal cortex of mice, socially isolated for 6 weeks, both neurosteroids were decreased by approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of the enzyme (5alpha-reductase Type I and II) that converts progesterone into 5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group-housed and socially isolated mice decreased exponentially to 10%-20% of control values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and 5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any given steady-state estimate the rate of synthesis required to maintain that steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis rates were decreased to 30% of the values calculated in group-housed mice. Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I mRNA and protein was approximately 50% lower than in group-housed mice whereas 3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups. Protracted social isolation in mice may provide a model to investigate whether 5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonists, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABA(A) receptors.
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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.