ArticleEndocrinology2006
Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors.
Article in Endocrinology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
150 citing papers in PubMed, 4 syntheses or guidelines pooled it, 366 citations in OpenAlex.
- Effects of Testosterone Replacement Therapy on Metabolic Syndrome in Male Patients-Systematic Review.International journal of molecular sciences · 2024Pooled it
- Non-alcoholic fatty liver disease across endocrinopathies: Interaction with sex hormones.Frontiers in endocrinology · 2022Pooled it
- Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies.Molecular metabolism · 2020Pooled it
- Intracrine and myotrophic roles of 5α-reductase and androgens: a review.Medicine and science in sports and exercise · 2012Pooled it
- Impaired adipogenesis and lipid storage capacity in subcutaneous adipose tissue of patients with PMOS.JCI insight · 2026Article
- Testosterone and cancers: biological functions, molecular mechanisms and therapy.Molecular cancer · 2026Review
- Reduced glycoprotein hormone β5 links male aging and testosterone decline to increased adiposity.The Journal of clinical investigation · 2026Article
- Metabolic Messengers: testosterone.Nature metabolism · 2026Review
- Adipose tissue and androgens: the ins and outs.Adipocyte · 2025Review
- Testosterone and Obesity in an Aging Society.Biomolecules · 2025Review
- Article
- The causal effects of genetically predicted sex hormone-binding globulin and sarcopenia: A 2-sample Mendelian randomization study.Medicine · 2025Article
- The role of androgens and global and tissue-specific androgen receptor expression on body composition, exercise adaptation, and performance.Biology of sex differences · 2025Review
- Loss of the APP regulator RHBDL4 preserves memory in an Alzheimer's disease mouse model.Cell death & disease · 2025Article
- Intracrine Formation of Steroid Hormones in Breast Cancer, Epidermal Keratinocyte, Dermal Fibroblast, and Adipocyte Cell Lines Measured by LC-MS/MS.International journal of molecular sciences · 2025Article
- Article
- Review
- Sexual Dimorphism's impact on adipogenesis: A three-dimensional in vitro model treated with 17β-estradiol and testosterone.Molecular and cellular endocrinology · 2024Article
- Testosterone Inhibits Lipid Accumulation in Porcine Preadipocytes by RegulatingAnimals : an open access journal from MDPI · 2024Article
- White adipocyte dysfunction and obesity-associated pathologies in humans.Nature reviews. Molecular cell biology · 2024Review
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Testosterone supplementation in men decreases fat mass; however, the mechanisms by which it inhibits fat mass are unknown. We hypothesized that testosterone inhibits adipogenic differentiation of preadipocytes by activation of androgen receptor (AR)/beta-catenin interaction and subsequent translocation of this complex to the nucleus thereby bypassing canonical Wnt signaling. We tested this hypothesis in 3T3-L1 cells that differentiate to form fat cells in adipogenic medium. We found that these cells express AR and that testosterone and dihydrotestosterone dose-dependently inhibited adipogenic differentiation as analyzed by Oil Red O staining and down-regulation of CCAAT/enhancer binding protein-alpha and -delta and peroxisome proliferator-activated receptor-gamma2 protein and mRNA. These inhibitory effects of androgens were partially blocked by flutamide or bicalutamide. Androgen treatment was associated with nuclear translocation of beta-catenin and AR. Immunoprecipitation studies demonstrated association of beta-catenin with AR and T-cell factor 4 (TCF4) in the presence of androgens. Transfection of TCF4 cDNA inhibited adipogenic differentiation, whereas a dominant negative TCF4 cDNA construct induced adipogenesis and blocked testosterone's inhibitory effects. Our gene array analysis indicates that testosterone treatment led to activation of some Wnt target genes. Expression of constitutively activated AR fused with VP-16 did not inhibit the expression of CCAAT/enhancer binding protein-alpha in the absence of androgens. Testosterone and dihydrotestosterone inhibit adipocyte differentiation in vitro through an AR-mediated nuclear translocation of beta-catenin and activation of downstream Wnt signaling. These data provide evidence for a regulatory role for androgens in inhibiting adipogenic differentiation and a mechanistic explanation consistent with the observed reduction in fat mass in men treated with androgens.
Indexed as
Identifiers
What OpenQuestion holds
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.