The DOI matches its Crossref record; 148 of the 151 references it cites were found in a registry or an index.
Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties
Abstract
Steroids influence neuronal function through binding to cognate intracellular receptors which may act as transcription factors in the regulation of gene expression. In addition, certain so-called neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially distinct 3alpha-reduced metabolites of progesterone and deoxycorticosterone are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABA(A)) receptors. However, also classical steroid hormones such as 17beta-estradiol, testosterone and progesterone are neuroactive steroids because they may act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT(3)) receptor, a ligand-gated ion channel or distinct glutamate receptors. A structure-activity relationship for the actions of a variety of steroids at the 5-HT(3) receptor was elaborated that differed considerably from that known for GABA(A) receptors. Although a bindings site for steroids at GABA(A) receptors is still a matter of debate, meanwhile there is also evidence that steroids interact allosterically with ligand-gated ion channels at the receptor membrane interface. On the other hand, also 3alpha-reduced neuroactive steroids may regulate gene expression via the progesterone receptor after intracellular oxidation into 5alpha-pregnane steroids. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose-dependent fashion in male Wistar rats. Moreover, progesterone and 3alpha-reduced neuroactive steroids produce a benzodiazepine-like sleep EEG profile in rats and humans. During major depression, there is a disequilibrium of such 3alpha-reduced neuroactive steroids which is corrected by successful treatment with antidepressant drugs. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. Studies in patients with panic disorder suggest that neuroactive steroids may also play a role in modulating human anxiety. Both the genomic and non-genomic effects of steroids in the brain may contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may represent a new treatment strategy for neuropsychiatric disorders.
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1 retracted
Dehydroepiandrosterone (DHEA) supplementation for cognitive function.
Huppert, F., & Van Niekerk, J. (2001) · The Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000304 · Cited by 88
RetractedThe Steroid and Thyroid Hormone Receptor Superfamily
Evans, R. M. (1988) · Science · doi:10.1126/science.3283939 · Cited by 7,394
Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor
Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., & Paul, S. M. (1986) · Science · doi:10.1126/science.2422758 · Cited by 2,225
An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway
Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80900-9 · Cited by 1,534
Paul, S. M., & Purdy, R. H. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.6.1347506 · Cited by 1,413
Primary Structure And Functional Expression of the 5HT 3 Receptor, A Serotonin-gated Ion Channel
Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R., & Julius, D. J. (1991) · Science · doi:10.1126/science.1718042 · Cited by 978
St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor
Moore, L. B., Goodwin, B. J., Jones, S. A., Wisely, G. B., Serabjit‐Singh, C. J., Willson, T. M., Collins, J. L., & Kliewer, S. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130155097 · Cited by 946
Neurosteroids: biosynthesis and function of these novel neuromodulators
Compagnone, N. A., & Mellon, S. H. (2000) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0188 · Cited by 820
Neurosteroids and GABAA receptor function
Lambert, J. J., Belelli, D., Hill-Venning, C., & Peters, J. A. (1995) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)89058-6 · Cited by 746
Steroid Hormone Receptors: Interaction with Deoxyribonucleic Acid and Transcription Factors*
Truss, M., & Beato, M. (1993) · Endocrine Reviews · doi:10.1210/edrv-14-4-459 · Cited by 739
Research works printed but not linked: 3
- Carter, 1997, Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3α-hydroxy-3-methyl-5α-pregnan-20-one), a selective high-affinity steroid modulator of the GABAA receptor, J. Pharmacol. Exp. Ther., 280, 1284
- Monteleone, 2000, Allopregnanlone concentrations and premenstrual syndrome, Eur, J. Endocrinol., 142, 269
- Ströhle, A., Romeo, E., di Michele, F., Pasini, A., Hermann, B., Gajewski, G., Holsboer, F., Rupprecht, R. Induced panic attacks shift GABAA receptor modulatory steroid composition in patients with panic disorder: preliminary results. Arch. Gen. Psychiatry, in press.
Cited by
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Items 401–428 of 428
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Mellon, S. H., Gong, W., & Schonemann, M. D. (2011) · Wiley eBooks · doi:10.1002/9783527633968.ch4
Habib, P., Neulen, J., Habib, S. A. J., & Rösing, B. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00541-2
Tolerance and antagonism to allopregnanolone effects in the rat CNS
Türkmen, Ş. (2006) · DiVA at Umeå University (Umeå University)
Habib, P., Neulen, J., Habib, S. A. J., & Rösing, B. (2020) · Research Square · doi:10.21203/rs.3.rs-62219/v1
Can hormones get you down? studies on sex steroids and depression
de Wit, A. E. (2021) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.178483963
Steiger, A. (2021) · Reference Module in Neuroscience and Biobehavioral Psychology · doi:10.1016/b978-0-12-378610-4.00115-7 · Cited by 1
Pharmacological Modeling and Regulation of Excitatory Amino Acid Transporters (EAATs)
Agarwal, S. R. (2007) · The Mathematics Enthusiast
Neurochemistry of Endogenous Antinociception
Horváth, G. (2010) · Advances in neurobiology · doi:10.1007/978-1-4419-7104-3_15
Psychoneuroendokrinologische und psychoneuroimmunologische Grundlagen psychischer Erkrankungen
Rupprecht, R., & Müller, N. (2011) · Springer eBooks · doi:10.1007/978-3-642-03637-8_9
Self-citationMorrow, A. L., & Porcu, P. (2014) · Springer eBooks · doi:10.1007/978-3-642-27772-6_280-2
Morrow, A. L., & Porcu, P. (2015) · Springer eBooks · doi:10.1007/978-3-642-36172-2_280
Porcu, P., O’Buckley, T. K., Song, S. C., Rokita, J. L., Lu, L., Wang, X., Williams, R. W., Miles, M. F., & Morrow, A. L. (2011) · PLoS ONE · doi:10.1371/annotation/ce7007ca-506f-4b54-b7ff-1e0a93d689f7
Rupprecht, R. (2011) · Springer eBooks · doi:10.1007/978-3-642-19844-1_20
Self-citationPsychoneuroendokrinologische Grundlagen psychischer Erkrankungen
Rupprecht, R. (2015) · Springer eBooks · doi:10.1007/978-3-642-45028-0_9-1
Self-citationMorrow, A. L., & Porcu, P. (2010) · Springer eBooks · doi:10.1007/978-3-540-68706-1_280
Fox, H. C., Milivojevic, V., & Sinha, R. (2023) · Handbook of experimental pharmacology · doi:10.1007/164_2023_687 · Cited by 1
Bubeníková, A., Máčová, L., Skalický, P., Mládek, A., & Bradáč, O. (2023) · Springer eBooks · doi:10.1007/978-3-031-36522-5_15
Welling, L. L. M., Mitchell, V. E., Lunge, J., & Hughes, M. (2024) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780197544754.013.46
Women’s Brain Health and Aging through the Lifespan
(2025) · Frontiers research topics · doi:10.3389/978-2-8325-6074-7
Raafat, M. A., Al-Hasnaawei, S., Mousa, H. M., Malathi, H., Sahu, S., Prathiba, S., Singh, G., & Sinha, A. (2026) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70673
Tiranini, L., Martella, S., Cucinella, L., Piccinino, M., Rossini, R., Martini, E., Stincardini, G., Bosoni, D., Righi, A., & Nappi, R. E. (2026) · Springer eBooks · doi:10.1007/978-3-032-05381-7_81
Riebel, M., Brunner, L.-M., Melchner, D., Doerfelt, A., Schwarzbach, J. V., Rupprecht, R., & Nothdurfter, C. (2026) · Pharmacopsychiatry · doi:10.1055/a-2935-8784
Self-citationSteiger, A., Dimopoulou, C., & Stalla, G. K. (2010) · Elsevier eBooks · doi:10.1016/b978-3-437-24680-7.10073-x
HORMONAL MODULATION OF THE BEHAVIORAL EFFECTS OF TRAIZOLAM
Babalonis, S. L. (2010) · UKnowledge (University of Kentucky)
Tiagabina w zaburzeniach lękowych
Pawelczyk, M., Kaczorowska, B., & Przybyła, M. (2012) · DOAJ (DOAJ: Directory of Open Access Journals)
Testosterone, Dominance, and Depression in Recently Married Couples
Quiñones-Torres, G. I. (2021) · ScholarWorks@UMassAmherst (University of Massachusetts Amherst) · doi:10.7275/5443197
Metadata
- Authors
- Rupprecht, R.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Rupprecht, R.
- ORCID
- Rupprecht, R.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 28
- Issue
- 2
- Pages
- 139-168
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2047844288
- Cited by
- 427
- References
- 151
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 12 · 2023: 14 · 2022: 13 · 2021: 6 · 2020: 11 · 2019: 14 · 2018: 13 · 2017: 6 · 2016: 13 · 2015: 18 · 2014: 14 · 2013: 18 · 2012: 26
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- neurosteroids, progesterone, deoxycorticosterone, GABA-A receptor modulation, 5-HT3 receptor antagonism, glutamate receptors, non-genomic steroid action, steroid hormone receptors, locomotor activity, sleep EEG, depression, anxiety, ethanol withdrawal, panic disorder, antidepressants, mental illness
- MeSH terms
- Anesthesia, Animals, Anticonvulsants, Antidepressive Agents, Humans, Nervous System, Receptors, GABA-A, Receptors, Serotonin, Sleep, Steroids, Antipsychotic Agents, Anti-Anxiety Agents, Gene Expression, Receptors, Neurotransmitter
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