ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
5α-Reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in rats.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Baseline vagal tone and pain reactivity: linking autonomic function to endogenous pain inhibition in women.Pain reports · 2026Article
- Maternal Milk Allopregnanolone May Buffer Negative Associations Between Maternal Postpartum Psychological Distress and Infant Regulatory Capacity.Developmental psychobiology · 2026Article
- Article
- Neurosteroid [3α,5α]-3-hydroxy-pregnan-20-one enhances IL-10 production via endosomal TRIF-dependent TLR4 signaling pathway.Frontiers in endocrinology · 2023Article
- Evaluating different models of maternal stress on stress-responsive systems in prepubertal mice.Frontiers in neuroscience · 2023Article
- Maternal glucocorticoids do not directly mediate the effects of maternal social stress on the fetus.The Journal of endocrinology · 2022Article
- Neurosteroids and early-life programming: An updated perspective.Current opinion in endocrine and metabolic research · 2022Article
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance.Frontiers in behavioral neuroscience · 2022Review
- Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes.Frontiers in pediatrics · 2021Review
- Effects of prenatal stress on neuroactive steroid responses to acute stress in adult male and female rats.Journal of neuroendocrinology · 2021Article
- Maternal Distress and Offspring Neurodevelopment: Challenges and Opportunities for Pre-clinical Research Models.Frontiers in human neuroscience · 2021Article
- Pubertal adversity alters chromatin dynamics and stress circuitry in the pregnant brain.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions.Frontiers in behavioral neuroscience · 2020Review
- A Systematic Review and Meta-Analysis of Within-Person Changes in Cardiac Vagal Activity across the Menstrual Cycle: Implications for Female Health and Future Studies.Journal of clinical medicine · 2019Review
- Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart.The Journal of endocrinology · 2019Article
- Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Review
- Sex-dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress.Journal of neuroendocrinology · 2018Article
- Why monkeys do not get multiple sclerosis (spontaneously): An evolutionary approach.Evolution, medicine, and public health · 2018Review
- Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.Dialogues in clinical neuroscience · 2016Review
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β-androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the "programmed" hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1β (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3β-diol normalized HPA axis responses to IL-1β in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5α-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1β. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5α-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner.
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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.