ArticleProceedings of the National Academy of Sciences of the United States of America2000
Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 134 citations in OpenAlex.
- Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts.The Journal of allergy and clinical immunology · 2015Trial
- A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Trial
- Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.Psychopharmacology · 2014Trial
- Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2009Trial
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- The gut-microbiota-brain axis: Focus on gut steroids.Journal of neuroendocrinology · 2025Review
- Neurosteroids: a lifelong impact on brain health.Frontiers in behavioral neuroscience · 2025Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells.Frontiers in immunology · 2023Article
- Review
- The steroidogenic inhibitor finasteride reverses pramipexole-induced alterations in probability discounting.Brain research bulletin · 2022Article
- Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.Journal of neuroendocrinology · 2022Review
- More than a marker: potential pathogenic functions of MAP2.Frontiers in molecular neuroscience · 2022Article
- Article
- Steroids and TRP Channels: A Close Relationship.International journal of molecular sciences · 2020Review
- Neuroprotective actions of cerebellar and pineal allopregnanolone on Purkinje cells.FASEB bioAdvances · 2020Review
- Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings.Journal of Alzheimer's disease reports · 2019Review
- Steroids and Brain, a Rising Bio-Medical Domain: a Perspective.Frontiers in endocrinology · 2018Article
- Potential Role of Microtubule Stabilizing Agents in Neurodevelopmental Disorders.International journal of molecular sciences · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fetal or adult rat-brain cytosol and fetal rat-brain microtubules contain a high-affinity, low-capacity pregnenolone-binding protein. The equilibrium dissociation constant is in the 30-50 nM range. The best competitors (in decreasing order) are pregnenolone sulfate, progesterone, Delta5-pregnene-3beta,20alpha-diol, and 3beta-hydroxy-5alpha-pregnan-20-one. It was hypothesized that the pregnenolone-binding protein pertained to microtubule-associated proteins (MAPs). Indeed, partial purification of fetal brain cytosol by fast pressure liquid chromatography with sequential ion-exchange and gel-filtration columns yielded two fractions, one of very high molecular mass, >200 kDa, and the other of 40-60 kDa, enriched in [(3)H]pregnenolone-binding activity and in proteins immunolabeled with monoclonal anti-tubulin and anti-MAP2 antibodies. Because many proteins are associated with microtubules, binding assays were repeated with purified calf-brain tubulin, MAP2, and Tau protein. Only the MAP2 fraction showed saturable [(3)H]pregnenolone binding with an affinity very close to that of rat-brain microtubules, but with a much larger concentration of binding sites (16 pmol/mg MAP2), which was increased more than 8-fold after copolymerization of MAP2 with tubulin. Finally, steroid effects on microtubule-assembly kinetics were assayed. Pregnenolone induced a large, dose-related increase of both the rate and extent of MAP2-induced tubulin assembly, whereas progesterone, inactive per se, counteracted the stimulatory effect of pregnenolone. Electron microscopic analysis confirmed that pregnenolone-increased assembly of microtubules produced a completely normal structure. The stimulatory effect on MAP2-tubulin interaction was also observed in fetal rat-brain neuron cultures. Therefore, we propose a mechanism of neurosteroid action, the control of microtubule or, more generally, of neural cytoskeleton dynamics, with potential roles in brain development, plasticity, and aging.
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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.