Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (821 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A 21-carbon steroid, derived from cholesterol and found in steroid hormone-producing tissues. Pregnenolone is the precursor to gonadal steroid hormones and the adrenal corticosteroids.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: 5-Pregnen-3-beta-ol-20-one; 5 Pregnen 3 beta ol 20 one.
Where it fits in the MeSH classification
- Broader topics
- Pregnenes; Hydroxycorticosteroids; Progesterone Congeners
- Narrower topics
- 17-alpha-Hydroxypregnenolone; Pregnenolone Carbonitrile
Related concepts
- Cholesterol
- Gonadal Steroid Hormones
- Corticosteroids
Research landscape
PubMed indexes 5,251 records tagged with the MeSH heading “Pregnenolone” (counts retrieved 2026-10-31). 199 of them (3.8%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,853 records.
Reviews account for 224 records (4.3%) and meta-analyses for 0. Randomized controlled trials number 30 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,853 |
| 2000-2009 | 660 |
| 2010-2019 | 539 |
| 2020 onward | 199 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 224 | 4.3% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 30 | 0.6% |
Method: PubMed query "Pregnenolone"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis | 2014 | Research article Design not recorded in structured metadata | 192 | cc by PMID 24813893 · DOI · PMC4039991 |
| Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice | 2012 | Research article Design not recorded in structured metadata | 49 | cc by PMID 22723881 · DOI · PMC3377726 |
| Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat | 2017 | Research article Design not recorded in structured metadata | 42 | cc by PMID 28665486 · DOI · PMC5601180 |
| Guanine and pregnenolone sulfate are associated with incident type 2 diabetes in two independent populations | 2025 | Research article Design not recorded in structured metadata | 2 | cc by PMID 41416067 · DOI · PMC12708234 |
Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- T helper 2 (Th2) cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines.
- Closing excerpt
- We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
T helper 2 (Th2) cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a "lymphosteroid," a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 24813893 · DOI · PMC4039991
Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis.
- Closing excerpt
- These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (253 words)
Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN) in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues. RT-PCR analysis of genes involved in gluconeogenesis, lipid metabolism and energy homeostasis reveal that PCN treatment on high-fat diet-fed mice reduces expression in the liver of G6Pase, Pepck, Cyp7a1, Cd36, L-Fabp, Srebp, and Fas genes and slightly enhances expression of Cyp27a1 and Abca1 genes. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue show that PCN treatment reduces expression of Pparγ2, Acc1, Cd36, but increases expression of Cpt1b and Pparα genes in mice fed with high-fat diet. Similarly, PCN treatment of animals on high-fat diet increases expression in brown adipose tissue of Pparα, Hsl, Cpt1b, and Cd36 genes, but reduces expression of Acc1 and Scd-1 genes. PXR activation by PCN in high-fat diet fed mice also increases expression of genes involved in thermogenesis in brown adipose tissue including Dio2, Pgc-1α, Pgc-1β, Cidea, and Ucp-3. These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 22723881 · DOI · PMC3377726
Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism.
- Closing excerpt
- Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (217 words)
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the 3 H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28665486 · DOI · PMC5601180
Guanine and pregnenolone sulfate are associated with incident type 2 diabetes in two independent populations [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundType 2 diabetes (T2D) is increasing its burden worldwide; therefore, research focused on its prediction and prevention is essential.
- Closing excerpt
- ConclusionWe identified significant associations of guanine, pregnenolone sulfate, and citrulline with incident T2D.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (198 words)
BackgroundType 2 diabetes (T2D) is increasing its burden worldwide; therefore, research focused on its prediction and prevention is essential.MethodsWe performed an untargeted metabolomics analysis using ultra high-performance liquid chromatography-mass spectrometry to discover metabolic biomarkers and biological pathways associated with incident T2D with a nested case-control design, followed by validation with targeted metabolomics in an independent cohort. In the discovery phase, plasma samples from 352 subjects (209 controls and 143 incident cases) were analyzed, collected with a mean (standard deviation) of 7.40 (0.76) years before they acquired the condition. Using this discovery phase cohort, six metabolites were identified using standards and were subsequently quantified in an independent validation phase cohort of 2,044 subjects (167 incident cases). Additionally, pathway enrichment was conducted in the discovery cohort.ResultsGuanine, ecgonine, adenine, pregnenolone sulfate, phenyl sulfate, and citrulline were significantly associated with incident T2D in at least one of the analyses performed in the discovery phase. Among these, guanine, pregnenolone sulfate, and citrulline maintained their significant associations with incident T2D in the validation cohort. Additionally, several pathways were significantly altered, with nucleotide metabolism and ABC transporter pathways among the most consistently affected.ConclusionWe identified significant associations of guanine, pregnenolone sulfate, and citrulline with incident T2D.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41416067 · DOI · PMC12708234
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Neurosteroids: beginning of the story [5]
- Research article Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging [6]
- Research article Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain [7]
- Research article Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence [8]
- Research article Neurosteroids and potential therapeutics: Focus on pregnenolone [9]
- Research article PRESENT STATUS OF RESEARCH ON CATABOLISM AND EXCRETION OF CHOLESTEROL [10]
References
- Mahata B, Zhang X, Kolodziejczyk AA, Proserpio V, Haim-Vilmovsky L, Taylor AE, et al.. Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. . 2014. PMID 24813893 · DOI · PMC4039991
- Ma Y, Liu D. Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice. . 2012. PMID 22723881 · DOI · PMC3377726
- Qaiser MZ, Dolman DEM, Begley DJ, Abbott NJ, Cazacu-Davidescu M, Corol DI, et al.. Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat. . 2017. PMID 28665486 · DOI · PMC5601180
- Barranco-Altirriba M, Granado-Casas M, Yanes O, Capellades J, Junza A, Franch-Nadal J, et al.. Guanine and pregnenolone sulfate are associated with incident type 2 diabetes in two independent populations. . 2025. PMID 41416067 · DOI · PMC12708234
- Baulieu EE, Robel P, Schumacher M. Neurosteroids: beginning of the story. Int Rev Neurobiol. 2001. PMID 11599297 · DOI
- Vallée M, Mayo W, Le Moal M. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev. 2001. PMID 11744095 · DOI
- Akwa Y, Young J, Kabbadj K, Sancho MJ, Zucman D, Vourc'h C, et al.. Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain. J Steroid Biochem Mol Biol. 1991. PMID 1835645 · DOI
- Marx CE, Bradford DW, Hamer RM, Naylor JC, Allen TB, Lieberman JA, et al.. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience. 2011. PMID 21756978 · DOI
- Vallée M. Neurosteroids and potential therapeutics: Focus on pregnenolone. J Steroid Biochem Mol Biol. 2016. PMID 26433186 · DOI
- DANIELSSON H. PRESENT STATUS OF RESEARCH ON CATABOLISM AND EXCRETION OF CHOLESTEROL. Adv Lipid Res. 1963. PMID 14248956 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.