Testosterone Inhibits Adipogenic Differentiation in 3T3-L1 Cells: Nuclear Translocation of Androgen Receptor Complex with β-Catenin and T-Cell Factor 4 May Bypass Canonical Wnt Signaling to Down-Regulate Adipogenic Transcription Factors
Open accessAbstract
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)/β-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-α and -δ and peroxisome proliferator-activated receptor-γ2 protein and mRNA. These inhibitory effects of androgens were partially blocked by flutamide or bicalutamide. Androgen treatment was associated with nuclear translocation of β-catenin and AR. Immunoprecipitation studies demonstrated association of β-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-α in the absence of androgens. Testosterone and dihydrotestosterone inhibit adipocyte differentiation in vitro through an AR-mediated nuclear translocation of β-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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Testosterone inhibits the expression of the activity of lipoprotein lipase, the main enzymatic regulator of triglyceride uptake in the fat cell, preferentially in abdominal fat.
“Testosterone inhibits the expression of the activity of lipoprotein lipase, the main enzymatic regulator of triglyceride uptake in the fat cell, preferentially in abdominal fat (28, 29).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964 · see citing works
Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183 · see citing works
Wnt signaling: a common theme in animal development
Cadigan, K. M., & Nusse, R. (1997) · Genes & Development · doi:10.1101/gad.11.24.3286 · Cited by 2,567 · see citing works
Convergence of Wnt, ß-Catenin, and Cadherin Pathways
Nelson, W. J., & Nusse, R. (2004) · Science · doi:10.1126/science.1094291 · Cited by 2,515 · see citing works
Understanding Adipocyte Differentiation
Gregoire, F. M., Smas, C. M., & Sul, H. S. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.3.783 · Cited by 2,358 · see citing works
Inhibition of Adipogenesis by Wnt Signaling
Ross, S. E., Hemati, N., Longo, K. A., Bennett, C. N., Lucas, P. C., Erickson, R. L., & MacDougald, O. A. (2000) · Science · doi:10.1126/science.289.5481.950 · Cited by 1,876 · see citing works
Secreted antagonists of the Wnt signalling pathway
Kawano, Y., & Kypta, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00623 · Cited by 1,584 · see citing works
C/EBPα induces adipogenesis through PPARγ: a unified pathwayPreprint
Rosen, E. D., Hsu, C.-H., Wang, X., Sakai, S., Freeman, M. W., Gonzalez, F. J., & Spiegelman, B. M. (2002) · Genes & Development · doi:10.1101/gad.948702 · Cited by 1,497 · see citing works
Biological Actions of Androgens
MOORADIAN, A. D., MORLEY, J. E., & KORENMAN, S. G. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-1-1 · Cited by 1,080 · see citing works
TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION DURING ADIPOCYTE DIFFERENTIATION
MacDougald, O. A., & Lane, M. D. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.002021 · Cited by 1,064 · see citing works
Testosterone dose-response relationships in healthy young men
Bhasin, S., Woodhouse, L., Casaburi, R., Singh, A. B., Bhasin, D., Berman, N., Chen, X., Yarasheski, K. E., Magliano, L., Dzekov, C., et al. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.6.e1172 · Cited by 967 · see citing works
Self-citationFearnhead, N. S. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.721 · Cited by 882 · see citing works
Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells
Green, H., & Kehinde, O. (1976) · Cell · doi:10.1016/0092-8674(76)90260-9 · Cited by 833 · see citing works
Regulation of Wnt Signaling during Adipogenesis
Bennett, C. N., Ross, S. E., Longo, K. A., Bajnok, L., Hemati, N., Johnson, K. W., Harrison, S. D., & MacDougald, O. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204527200 · Cited by 743 · see citing works
Yeh, S., Tsai, M.-Y., Xu, Q., Mu, X., Lardy, H. A., Huang, K., Lin, H., Yeh, S.-D., Altuwaijri, S., Zhou, X., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212474399 · Cited by 668 · see citing works
Effects of Testosterone Replacement in Hypogonadal Men1
Snyder, P. J., Peachey, H., Berlin, J. A., Hannoush, P., Haddad, G., Dlewati, A., Santanna, J., Loh, L., Lenrow, D. A., Holmes, J. H., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6731 · Cited by 608 · see citing works
Singh, R., Artaza, J. N., Taylor, W. E., Gonzalez-Cadavid, N. F., & Bhasin, S. (2003) · Endocrinology · doi:10.1210/en.2003-0741 · Cited by 555 · see citing works
Self-citationThe effects of testosterone treatment on body composition and metabolism in middle-aged obese men.
Mårin, P., Holmäng, S., Jönsson, L., Sjöström, L., Kvist, H., Holm, G., Lindstedt, G., & Björntorp, P. A. (1992) · PubMed · Cited by 553 · see citing works
Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men 1
Bhasin, S., Storer, T. W., Berman, N., Yarasheski, K. E., Clevenger, B., Phillips, J., Lee, W. P., Bunnell, T. J., & Casaburi, R. H. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3733 · Cited by 540 · see citing works
Self-citationEffect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age
Snyder, P. J. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.8.2647 · Cited by 531 · see citing works
Expression of CD44 in Apc and TcfMutant Mice Implies Regulation by the WNT Pathway
Wielenga, V. T., Smits, R., Kořínek, V., Smit, L., Kielman, M. F., Fodde, R., Clevers, H. C., & Pals, S. T. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65297-2 · Cited by 512 · see citing works
Effects of Testosterone Replacement in Hypogonadal Men
Snyder, P. J. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2670 · Cited by 464 · see citing works
β-catenin–sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer
Hovanes, K., Li, T. W. H., Munguia, J. E., Truong, T., Milovanović, T., Marsh, J., Holcombe, R. F., & Waterman, M. L. (2001) · Nature Genetics · doi:10.1038/ng0501-53 · Cited by 458 · see citing works
Brodsky, I. G., Balagopal, P., & Nair, K. S. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.10.8855787 · Cited by 444 · see citing works
Wilson, J. D. (1988) · Endocrine Reviews · doi:10.1210/edrv-9-2-181 · Cited by 427 · see citing works
Mauras, N., Hayes, V. Y., Welch, S., Rini, A., Helgeson, K., Dokler, M. L., Veldhuis, J. D., & Urban, R. J. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4892 · Cited by 409 · see citing works
A transcriptional response to Wnt protein in human embryonic carcinoma cells
Willert, J. R., Epping, M. T., Pollack, J. R., Brown, P. O., & Nusse, R. (2002) · BMC Developmental Biology · doi:10.1186/1471-213x-2-8 · Cited by 398 · see citing works
Wnt10b Inhibits Development of White and Brown Adipose Tissues
Longo, K. A., Hahn, W. S., Kang, S., Gerin, I., Chiang, S.-H., Lucas, P. C., Opp, M. R., & MacDougald, O. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402937200 · Cited by 372 · see citing works
Bhasin, S. (2000) · JAMA · doi:10.1001/jama.283.6.763 · Cited by 367 · see citing works
Self-citationBeta-catenin affects androgen receptor transcriptional activity and ligand specificity.
Truica, C. I., Byers, S. W., & Gelmann, E. P. (2000) · PubMed · Cited by 349 · see citing works
Linking β-Catenin to Androgen-signaling Pathway
Yang, F., Li, X., Sharma, M., Sasaki, C. Y., Longo, D. L., Lim, B., & Sun, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111962200 · Cited by 342 · see citing works
Mårin, P., Odén, B., & Björntorp, P. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.1.7829619 · Cited by 332 · see citing works
Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men
Bhasin, S. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.2.407 · Cited by 318 · see citing works
Self-citationWnt signaling and the activation of myogenesis in mammals
Cossu, G., & Borello, U. (1999) · The EMBO Journal · doi:10.1093/emboj/18.24.6867 · Cited by 312 · see citing works
The subcellular destinations of apc proteins
Bienz, M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm806 · Cited by 243 · see citing works
Effects of Androgen Administration in Men with the AIDS Wasting Syndrome
Grinspoon, S. K., Corcoran, C. P., Askari, H., Schoenfeld, D., Wolf, L., Burrows, B. A., Walsh, M. J., Hayden, D., Parlman, K., Anderson, E., et al. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-1-199807010-00005 · Cited by 234 · see citing works
Dieudonné, M., Pecquery, R., Leneveu, M.-C., & Giudicelli, Y. (2000) · Endocrinology · doi:10.1210/endo.141.2.7293 · Cited by 219 · see citing works
Dieudonné, M., Pecquery, R., Boumédiène, A., Leneveu, M.-C., & Giudicelli, Y. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.6.c1645 · Cited by 197 · see citing works
Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues.
Mårin, P., Krotkiewski, M., & Björntorp, P. A. (1992) · PubMed · Cited by 196 · see citing works
Lu, S., Liu, M., Epner, D. E., Tsai, S. Y., & Tsai, M. (1999) · Molecular Endocrinology · doi:10.1210/mend.13.3.0254 · Cited by 185 · see citing works
Mulholland, D. J., Cheng, H., Reid, K. J., Rennie, P. S., & Nelson, C. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200135200 · Cited by 173 · see citing works
Liganded Androgen Receptor Interaction with β-Catenin
Pawlowski, J. E., Ertel, J. R., Allen, M. P., Xu, M., Butler, C., Wilson, E. M., & Wierman, M. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200545200 · Cited by 166 · see citing works
Hemati, N., Ross, S. E., Erickson, R. L., Groblewski, G. E., & MacDougald, O. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.41.25913 · Cited by 159 · see citing works
Nuclear and cytoplasmic localizations of the adenomatous polyposis coli protein
Neufeld, K. L., & White, R. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.3034 · Cited by 122 · see citing works
Artaza, J. N., Bhasin, S., Mallidis, C., Taylor, W. E., Ma, K., & González-Cadavid, N. F. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10044 · Cited by 115 · see citing works
Self-citationSRY Interacts with and Negatively Regulates Androgen Receptor Transcriptional Activity
Yuan, X., Lu, M. L., Li, T., & Balk, S. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108404200 · Cited by 108 · see citing works
Self-citationRamirez, M. E., McMurry, M. P., Wiebke, G. A., Felten, K. J., Ren, K., Meikle, A. W., & Iverius, P. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90299-7 · Cited by 89 · see citing works
Wnt–frizzled signaling in the induction and differentiation of the neural crest
Yanfeng, W. A., Saint‐Jeannet, J., & Klein, P. S. (2003) · BioEssays · doi:10.1002/bies.10255 · Cited by 87 · see citing works
Androgen receptor functions from reverse genetic models
Μatsumoto, T., Takeyama, K., Sato, T., & Kato, S. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00231-0 · Cited by 77 · see citing works
Zhang, F., White, R. L., & Neufeld, K. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.23.8143-8156.2001 · Cited by 73 · see citing works
Specific Androgen Receptor Activation by an Artificial Coactivator
Sui, X., Bramlett, K. S., Jorge, M. C., Swanson, D. A., von Eschenbach, A. C., & Jenster, G. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.14.9449 · Cited by 35 · see citing works
Garcia, E., Lacasa, M., Agli, B., Giudicelli, Y., & Lacasa, D. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1610089 · Cited by 33 · see citing works
Flagged first, then by citations
4 of the 57 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Adipocyte differentiation from the inside out
Rosen, E. D., & MacDougald, O. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2066 · Cited by 2,607 · see citing works
Pope, H. G., Wood, R. I., Rogol, A. D., Nyberg, F., Bowers, L. D., & Bhasin, S. (2013) · Endocrine Reviews · doi:10.1210/er.2013-1058 · Cited by 663 · see citing works
Self-citationPower, M. L., & Schulkin, J. A. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507853347 · Cited by 610 · see citing works
Sanchez-Garrido, M. A., & Tena-Sempere, M. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.001 · Cited by 557 · see citing works
Transcriptional Regulation of Adipogenesis
de Sá, P. M., Richard, A. J., Hang, H., & Stephens, J. M. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160022 · Cited by 395 · see citing works
Wnt/β-catenin signaling in adipogenesis and metabolism
Prestwich, T. C., & MacDougald, O. A. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.09.014 · Cited by 355 · see citing works
Testosterone deficiency, insulin resistance and the metabolic syndrome
Zitzmann, M. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.212 · Cited by 353 · see citing works
Kalinchenko, S. Y., Tishova, Y. A., Mskhalaya, G. J., Gooren, L. J., Giltay, E. J., & Saad, F. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03845.x · Cited by 347 · see citing works
Brand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., & van der Schouw, Y. T. (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyq158 · Cited by 334 · see citing works
Mauvais-Jarvis, F. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.10.002 · Cited by 335 · see citing works
Sarjeant, K., & Stephens, J. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008417 · Cited by 328 · see citing works
Androgens and body fat distribution
Blouin, K., Boivin, A., & Tchernof, A. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.09.001 · Cited by 306 · see citing works
Bhasin, S., Calof, O. M., Storer, T. W., Lee, M. L., Mazer, N. A., Jasuja, R., Montori, V. M., Gao, W., & Dalton, J. T. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0120 · Cited by 300 · see citing works
Self-citationTestosterone and insulin resistance in the metabolic syndrome and T2DM in men
Rao, P. M., Kelly, D. M., & Jones, T. H. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.122 · Cited by 292 · see citing works
The role of androgens in metabolism, obesity, and diabetes in males and females
Navarro, G., Allard, C., Xu, W., & Mauvais‐Jarvis, F. (2015) · Obesity · doi:10.1002/oby.21033 · Cited by 289 · see citing works
Sex dimorphism and depot differences in adipose tissue function
White, U. A., & Tchoukalova, Y. D. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.006 · Cited by 281 · see citing works
Traish, A. M., Goldstein, I., & Kim, N. N. (2007) · European Urology · doi:10.1016/j.eururo.2007.02.034 · Cited by 268 · see citing works
Onset of effects of testosterone treatment and time span until maximum effects are achieved
Saad, F., Aversa, A., Isidori, A. M., Zafalon, L., Zitzmann, M., & Gooren, L. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0221 · Cited by 232 · see citing works
Selective androgen receptor modulators as function promoting therapies
Bhasin, S., & Jasuja, R. (2009) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32832a3d79 · Cited by 223 · see citing works
Self-citationEndocrine Aspects of Male Sexual Dysfunctions
Buvat, J., Maggi, M., Gooren, L., Guay, A. T., Kaufman, J., Morgentaler, A., Schulman, C., Tan, H. M., Torres, L. O., Yassin, A., et al. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.01780.x · Cited by 221 · see citing works
White adipocyte dysfunction and obesity-associated pathologies in humans
Hagberg, C. E., & Spalding, K. L. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00680-1 · Cited by 217 · see citing works
Traish, A. M., Miner, M. M., Morgentaler, A., & Zitzmann, M. (2011) · The American Journal of Medicine · doi:10.1016/j.amjmed.2010.12.027 · Cited by 206 · see citing works
Bone and muscle loss after spinal cord injury: organ interactions
Qin, W., Bauman, W. A., & Cardozo, C. P. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05806.x · Cited by 189 · see citing works
Traish, A. M., Haider, A., Doros, G. D., & Saad, F. (2013) · International Journal of Clinical Practice · doi:10.1111/ijcp.12319 · Cited by 187 · see citing works
A small-molecule inhibitor of Tcf/β-catenin signaling down-regulates PPARγ and PPARδ activities
Handeli, S., & Simon, J. A. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-2063 · Cited by 183 · see citing works
Corbould, A. (2007) · Journal of Endocrinology · doi:10.1677/joe.1.07070 · Cited by 184 · see citing works
Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise
Kraemer, W. J., Ratamess, N. A., & Nindl, B. C. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00599.2016 · Cited by 181 · see citing works
Endocrinology of the aging male
de Araújo, A. B., & Wittert, G. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.11.004 · Cited by 180 · see citing works
Understanding androgen action in adipose tissue
O’Reilly, M. W., House, P. J., & Tomlinson., J. W. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.04.008 · Cited by 180 · see citing works
Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation
Chazenbalk, G. D., Singh, P., Irge, D., Shah, A., Abbott, D. H., & Dumesic, D. A. (2013) · Steroids · doi:10.1016/j.steroids.2013.05.001 · Cited by 167 · see citing works
Cellular models for understanding adipogenesis, adipose dysfunction, and obesity
Armani, A., Mammi, C., Marzolla, V., Calanchini, M., Antelmi, A., Rosano, G. M. C., Fabbri, A., & Caprio, M. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22598 · Cited by 166 · see citing works
Gupta, V., Bhasin, S., Guo, W., Singh, R., Miki, R., Chauhan, P., Choong, K., Tchkonia, T., Lebrasseur, N. K., Flanagan, J. N., et al. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.08.019 · Cited by 162 · see citing works
Self-citationTestosterone in men with advanced liver disease: Abnormalities and implications
Sinclair, M. J., Grossmann, M., Gow, P. J., & Angus, P. (2014) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12695 · Cited by 160 · see citing works
Phenotypic heterogeneity of mutations in androgen receptor gene
Rajender, S., Singh, L., & Kumarasamy Thangaraj, K. (2007) · Asian Journal of Andrology · doi:10.1111/j.1745-7262.2007.00250.x · Cited by 158 · see citing works
Risks and benefits of testosterone therapy in older men
Spitzer, M., Huang, G., Basaria, S., Travison, T. G., & Bhasin, S. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.73 · Cited by 154 · see citing works
Self-citationObesity and late-onset hypogonadism
Corona, G., Vignozzi, L., Sforza, A., Mannucci, E., & Maggi, M. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.06.031 · Cited by 154 · see citing works
Saad, F., Aversa, A., M. Isidori, A., & J. Gooren, L. (2012) · Current Diabetes Reviews · doi:10.2174/157339912799424573 · Cited by 148 · see citing works
Androgen metabolism in adipose tissue: Recent advances
Blouin, K., Veilleux, A., Luu-The, V., & Tchernof, A. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.10.035 · Cited by 149 · see citing works
Lin, W., Xiang, L., Shi, H., Zhang, J., Jiang, L., Cai, P., Lin, Z., Lin, B., Huang, Y., Zhang, H., et al. (2015) · BioMed Research International · doi:10.1155/2015/730139 · Cited by 146 · see citing works
Corbould, A. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.872 · Cited by 143 · see citing works
Caprio, M., Antelmi, A., Chetrite, G., Muscat, A., Mammi, C., Marzolla, V., Fabbri, A., Zennaro, M., & Fève, B. (2010) · Endocrinology · doi:10.1210/en.2010-0674 · Cited by 139 · see citing works
Position Stand on Androgen and Human Growth Hormone Use
Hoffman, J. R., Kraemer, W. J., Bhasin, S., Storer, T. W., Ratamess, N. A., Haff, G. G., Willoughby, D. S., & Rogol, A. D. (2009) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e31819df2e6 · Cited by 140 · see citing works
Self-citationAdiponectin protects against development of metabolic disturbances in a PCOS mouse model
Benrick, A., Chanclón, B., Micallef, P., Wu, Y., Hadi, L., Shelton, J. M., Stener‐Victorin, E., & Asterholm, I. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1708854114 · Cited by 138 · see citing works
Singh, R., Bhasin, S., Braga, M., Artaza, J. N., Pervin, S., Taylor, W. E., Krishnan, V., Sinha, S. K., Rajavashisth, T. B., & Jasuja, R. (2008) · Endocrinology · doi:10.1210/en.2008-0858 · Cited by 131 · see citing works
Self-citationBlouin, K., Nadeau, M., Perreault, M., Veilleux, A., Drolet, R., Marceau, P., Mailloux, J. R., Luu‐The, V., & Tchernof, A. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03645.x · Cited by 131 · see citing works
Recent advances in the biology and therapy of muscle wasting
Glass, D. J., & Roubenoff, R. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05809.x · Cited by 127 · see citing works
McInnes, K. J., Smith, L. B., Hunger, N. I., Saunders, P. T. K., Andrew, R., & Walker, B. R. (2012) · Diabetes · doi:10.2337/db11-1136 · Cited by 121 · see citing works
A plural role for lipids in motor neuron diseases: energy, signaling and structure
Schmitt, F., Hussain, G., Dupuis, L., Loeffler, J., & Henriques, A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00025 · Cited by 120 · see citing works
Follistatin Promotes Adipocyte Differentiation, Browning, and Energy Metabolism
Braga, M., Reddy, S. T., Vergnes, L., Pervin, S., Grijalva, V., Stout, D., David, J., Li, X., Tomasian, V., Reid, C. B., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m039719 · Cited by 111 · see citing works
Self-citationWhich patients with sexual dysfunction are suitable for testosterone replacement therapy?
Morelli, A., Corona, G., Filippi, S., Ambrosini, S., Forti, G., Vignozzi, L., & Maggi, M. (2007) · Journal of Endocrinological Investigation · doi:10.1007/bf03349232 · Cited by 110 · see citing works
Adipose tissue expandability and the early origins of PCOS
de Zegher, F., López‐Bermejo, A., & Ibáñez, L. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.06.003 · Cited by 108 · see citing works
The triad of erectile dysfunction, hypogonadism and the metabolic syndrome
Shabsigh, R., Arver, S., Channer, K. S., Ian Eardley, C., Fabbri, A., Gooren, L. J., Heufelder, A. E., Jones, H., Meryn, S., & Zitzmann, M. (2008) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2008.01696.x · Cited by 105 · see citing works
Gebhardt, R., & Hovhannisyan, A. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22041 · Cited by 101 · see citing works
Androgens and metabolic syndrome: Lessons from androgen receptor knock out (ARKO) mice
Yanase, T., Fan, W., Kyoya, K., Min, L., Takayanagi, R., Kato, S., & Nawata, H. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.03.017 · Cited by 101 · see citing works
Regulation of Adipocyte Differentiation via MicroRNAs
Son, Y. H., Ka, S., Kim, A., & Kim, J. B. (2014) · Endocrinology and Metabolism · doi:10.3803/enm.2014.29.2.122 · Cited by 101 · see citing works
The Alliance of Mesenchymal Stem Cells, Bone, and Diabetes
Napoli, N., Strollo, R., Paladini, A., Briganti, S., Pozzilli, P., & Epstein, S. (2014) · International Journal of Endocrinology · doi:10.1155/2014/690783 · Cited by 99 · see citing works
Obesity phenotypes: depot-differences in adipose tissue and their clinical implications
Guglielmi, V., & Sbraccia, P. (2017) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-017-0467-9 · Cited by 97 · see citing works
Fetal origins of the metabolic syndrome
Xita, N., & Tsatsoulis, A. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05658.x · Cited by 96 · see citing works
Kaur, H., & Werstuck, G. H. (2021) · CJC Open · doi:10.1016/j.cjco.2021.05.007 · Cited by 98 · see citing works
Braga, M., Bhasin, S., Jasuja, R., Pervin, S., & Singh, R. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.11.019 · Cited by 96 · see citing works
Self-citationAndrogens and Adipose Tissue in Males: A Complex and Reciprocal Interplay
Mammi, C., Calanchini, M., Antelmi, A., Cinti, F., Rosano, G. M. C., Lenzi, A., Caprio, M., & Fabbri, A. (2012) · International Journal of Endocrinology · doi:10.1155/2012/789653 · Cited by 95 · see citing works
Rehan, V. K., Asotra, K., & Torday, J. S. (2009) · Lung · doi:10.1007/s00408-009-9158-2 · Cited by 93 · see citing works
Traish, A. M. (2014) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000086 · Cited by 94 · see citing works
Artaza, J. N., Sirad, F., Ferrini, M. G., & Norris, K. C. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.01.001 · Cited by 93 · see citing works
Self-citationKitagawa, T., Matsuda, K., Inui, S., Takenaka, H., Katoh, N., Itami, S., Kishimoto, S., & Kawata, M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1053 · Cited by 95 · see citing works
Blouin, K., Nadeau, M., Mailloux, J. R., Daris, M., Lebel, S., Luu-The, V., & Tchernof, A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00039.2008 · Cited by 92 · see citing works
Androgen inactivation and steroid-converting enzyme expression in abdominal adipose tissue in men
Blouin, K., Richard, C., Brochu, G., Hould, F.-S., Lebel, S., Marceau, S., Biron, S., Luu-The, V., & Tchernof, A. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06365 · Cited by 90 · see citing works
Zhao, J., Yue, W., Zhu, M. J., Sreejayan, N., & Du, . (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.161 · Cited by 90 · see citing works
Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements
Maneschi, E., Morelli, A., Filippi, S., Cellai, I., Comeglio, P., Mazzanti, B., Mello, T., Calcagno, A., Sarchielli, E., Vignozzi, L., et al. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0333 · Cited by 89 · see citing works
Impact of testosterone on body fat composition
Maddalena, C. D., Vodo, S., Petroni, A., & Aloisi, A. M. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24096 · Cited by 89 · see citing works
Androgens and the Regulation of Adiposity and Body Fat Distribution in Humans
Tchernof, A., Brochu, D., Maltais‐Payette, I., Mansour, M. F., Marchand, G. B., Carreau, A., & Kapeluto, J. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170009 · Cited by 110 · see citing works
Sex Hormones and Macronutrient Metabolism
Comitato, R., Saba, A., Turrini, A., Arganini, C., & Virgili, F. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2011.651177 · Cited by 83 · see citing works
Testosterone and type 2 diabetes
Grossmann, M., Gianatti, E. J., & Zajac, J. D. (2010) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e32833919cf · Cited by 108 · see citing works
Sex Steroid Hormone Levels and Body Composition in Men
Gates, M. A., Mekary, R. A., Chiu, G. R., Ding, E. L., Wittert, G., & de Araújo, A. B. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2582 · Cited by 84 · see citing works
Moreno‐Navarrete, J. M., & Fernández‐Real, J. M. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0965-6_2 · Cited by 83 · see citing works
Saad, F., & Gooren, L. J. (2010) · Journal of Obesity · doi:10.1155/2011/471584 · Cited by 81 · see citing works
Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review
Dandona, P., Dhindsa, S., Ghanim, H., & Saad, F. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14206 · Cited by 86 · see citing works
Ibebunjo, C., Eash, J. K., Li, C., Ma, Q., & Glass, D. J. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00402.2010 · Cited by 81 · see citing works
Sarcopenia and Androgens: A Link between Pathology and Treatment
Basualto-Alarcón, C., Varela, D., Duran, J., Maass, R., & Estrada, M. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00217 · Cited by 80 · see citing works
Amelioration of Penile Fibrosis: Myth or Reality
El‐Sakka, A. I., & Yassin, A. A. (2010) · Journal of Andrology · doi:10.2164/jandrol.109.008730 · Cited by 80 · see citing works
Androgen Effects on Adipose Tissue Architecture and Function in Nonhuman Primates
Varlamov, O., White, A. E., Carroll, J. M., Bethea, C. L., Reddy, A. P., Slayden, O. D., O’Rourke, R. W., & Roberts, C. T. (2012) · Endocrinology · doi:10.1210/en.2011-2111 · Cited by 74 · see citing works
Androgens Play a Pivotal Role in Maintaining Penile Tissue Architecture and Erection: A Review
Traish, A. M. (2009) · Journal of Andrology · doi:10.2164/jandrol.108.006007 · Cited by 75 · see citing works
Barbonetti, A., Caterina Vassallo, M. R., Cotugno, M., Felzani, G., Francavilla, S., & Francavilla, F. (2016) · The Journal of Spinal Cord Medicine · doi:10.1179/2045772314y.0000000288 · Cited by 75 · see citing works
Adiposopathy: why do adiposity and obesity cause metabolic disease?
Bays, H. E., & Ballantyne, C. M. (2006) · Future Lipidology · doi:10.2217/17460875.1.4.389 · Cited by 73 · see citing works
The use of phosphodiesterase 5 inhibitors with concomitant medications
Corona, G., Razzoli, E., Forti, G., & Maggi, M. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03349261 · Cited by 74 · see citing works
Updated survey of the steroid-converting enzymes in human adipose tissues
Tchernof, A., Mansour, M. F., Pelletier, M., Boulet, M.-M., Nadeau, M., & Luu-The, V. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.11.011 · Cited by 73 · see citing works
Nuclear receptor regulation of stemness and stem cell differentiation
Jeong, Y., & Mangelsdorf, D. J. (2009) · Experimental & Molecular Medicine · doi:10.3858/emm.2009.41.8.091 · Cited by 74 · see citing works
Testosterone metabolites differentially regulate obesogenesis and fat distribution
Sebo, Z. L., & Rodeheffer, M. S. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101141 · Cited by 71 · see citing works
Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men
Corona, G., Bianchini, S., Sforza, A., Vignozzi, L., & Maggi, M. (2015) · HORMONES · doi:10.14310/horm.2002.1635 · Cited by 70 · see citing works
Myocyte Androgen Receptors Increase Metabolic Rate and Improve Body Composition by Reducing Fat Mass
Fernando, S. M., Rao, P., Niel, L., Chatterjee, D., Stagljar, M., & Monks, D. A. (2010) · Endocrinology · doi:10.1210/en.2010-0018 · Cited by 69 · see citing works
Androgen activates β-catenin signaling in bladder cancer cells
Li, Y., Zheng, Y., Izumi, K., Ishiguro, H., Ye, B., Li, F., & Miyamoto, H. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0328 · Cited by 67 · see citing works
Cardoso, R. C., Veiga‐Lopez, A., Moeller, J., Beckett, E. M., Pease, A. P., Keller, E., Madrigal, V., Chazenbalk, G. D., Dumesic, D. A., & Padmanabhan, V. (2015) · Endocrinology · doi:10.1210/en.2015-1565 · Cited by 67 · see citing works
Yarrow, J. F., McCoy, S. C., & Borst, S. E. (2010) · Steroids · doi:10.1016/j.steroids.2010.01.019 · Cited by 65 · see citing works
Noh, T., Gabet, Y., Cogan, J. P., Shi, Y., Tank, A., Sasaki, T., Criswell, B., Dixon, A., Lee, C. S., Tam, J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005438 · Cited by 65 · see citing works
Liu, X., Allen, J. D., Arnold, J. T., & Blackman, M. R. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn011 · Cited by 65 · see citing works
Obesity attenuates gender differences in cardiovascular mortality
for the DECODE Study Group, Song, X., Tabák, Á. G., Zethelius, B., Yudkin, J. S., Söderberg, S., Laatikainen, T. K., Stehouwer, C. D. A., Dankner, R. S., Jousilahti, P., et al. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0144-5 · Cited by 64 · see citing works
Inhibition of in vitro and in vivo brown fat differentiation program by myostatin
Braga, M., Pervin, S., Norris, K. C., Bhasin, S., & Singh, R. (2013) · Obesity · doi:10.1002/oby.20117 · Cited by 64 · see citing works
Self-citationDeciphering the selective androgen receptor modulators paradigm
Zhang, X., & Sui, Z. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2013.741582 · Cited by 64 · see citing works
Kuo, D., Yeh, C., Shieh, P., Cheng, K., Chen, F., & Cheng, J. (2009) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2009.05.005 · Cited by 63 · see citing works
Veiga‐Lopez, A., Moeller, J., Patel, D., Ye, W., Pease, A. P., Kinns, J., & Padmanabhan, V. (2013) · Endocrinology · doi:10.1210/en.2012-2145 · Cited by 64 · see citing works
- Authors
- Singh, R., Artaza, J. N., Taylor, W. E., Braga, M., Yuan, X., Gonzalez-Cadavid, N. F., & Bhasin, S.
- Affiliations
- Charles R. Drew University of Medicine and Science (US)
- Beth Israel Deaconess Medical Center (US)
- Division of Endocrinology, Metabolism, and Molecular Medicine (R.S., J.N.A., W.E.T., M.B., N.F.G.-C., S.B.), Charles R. Drew University of Medicine and Science, Los Angeles, California 90059
- Boston Medical Center (US)
- Corresponding author
- Singh, Rajan
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-01-01
- Volume
- 147
- Issue
- 1
- Pages
- 141-154
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC4417624
- OpenAlex
- W2064549818
- Cited by
- 369
- References
- 57
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 13 · 2023: 5 · 2022: 14 · 2021: 6 · 2020: 17 · 2019: 7 · 2018: 13 · 2017: 27 · 2016: 9 · 2015: 30 · 2014: 20 · 2013: 29 · 2012: 21
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1p20md000545-01, 5u01dk070431-11)
- National Institute on Aging (SC1AG033407)
- National Institute of General Medical Sciences (S06GM068510)
- National Institute of Diabetes and Digestive and Kidney Diseases (1R01 DK 59627-01, U01-DK-070431, R01DK070534, R01DK059627, 1R01DK70431-01)
- National Center for Research Resources (G12 RR 03026, G12RR003026)
- National Institute on Minority Health and Health Disparities (1P20MD000545-02, P20 MD000545)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD041748-0, U54HD041748, R01HD043348)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- testosterone, adipogenesis, androgen receptor, β-catenin, T-cell factor 4, Wnt signaling, 3T3-L1 cells, preadipocytes, C/EBPα, C/EBPδ, PPARγ, nuclear translocation, flutamide, bicalutamide, fat mass, androgen supplementation
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Cell Nucleus, Gene Expression Regulation, Receptors, Androgen, RNA, Messenger, Testosterone, Transcription Factors, Transcription, Genetic, Signal Transduction, 3T3 Cells, Adipocytes, Reverse Transcriptase Polymerase Chain Reaction, Protein Transport, Wnt Proteins, beta Catenin, Mice, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
