Testosterone reduces metabolic brown fat activity in male mice

in Journal of Endocrinology
Authors:
Marta Lantero Rodriguez Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Marta Lantero Rodriguez in
Current site
Google Scholar
PubMed
Close
,
Maaike Schilperoort Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Search for other papers by Maaike Schilperoort in
Current site
Google Scholar
PubMed
Close
,
Inger Johansson Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Inger Johansson in
Current site
Google Scholar
PubMed
Close
,
Elin Svedlund Eriksson Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Elin Svedlund Eriksson in
Current site
Google Scholar
PubMed
Close
,
Vilborg Palsdottir Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Vilborg Palsdottir in
Current site
Google Scholar
PubMed
Close
,
Jan Kroon Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Search for other papers by Jan Kroon in
Current site
Google Scholar
PubMed
Close
,
Marcus Henricsson Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Marcus Henricsson in
Current site
Google Scholar
PubMed
Close
,
Sander Kooijman Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Search for other papers by Sander Kooijman in
Current site
Google Scholar
PubMed
Close
,
Mia Ericson Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Mia Ericson in
Current site
Google Scholar
PubMed
Close
,
Jan Borén Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Jan Borén in
Current site
Google Scholar
PubMed
Close
,
Claes Ohlsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Claes Ohlsson in
Current site
Google Scholar
PubMed
Close
,
John-Olov Jansson Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by John-Olov Jansson in
Current site
Google Scholar
PubMed
Close
,
Malin C Levin Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Malin C Levin in
Current site
Google Scholar
PubMed
Close
,
Patrick C N Rensen Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Search for other papers by Patrick C N Rensen in
Current site
Google Scholar
PubMed
Close
, and
Åsa Tivesten Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Åsa Tivesten in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-8318-0486

Correspondence should be addressed to Å Tivesten: asa.tivesten@medic.gu.se

*(M Lantero Rodriguez and M Schilperoort contributed equally to this work)

(V Palsdottir is now at AstraZeneca, Mölndal, Sweden)

Restricted access
Rent on DeepDyve

Sign up for journal news

Brown adipose tissue (BAT) burns substantial amounts of mainly lipids to produce heat. Some studies indicate that BAT activity and core body temperature are lower in males than females. Here we investigated the role of testosterone and its receptor (the androgen receptor; AR) in metabolic BAT activity in male mice. Castration, which renders mice testosterone deficient, slightly promoted the expression of thermogenic markers in BAT, decreased BAT lipid content, and increased basal lipolysis in isolated brown adipocytes. Further, castration increased the core body temperature. Triglyceride-derived fatty acid uptake, a proxy for metabolic BAT activity in vivo, was strongly increased in BAT from castrated mice (4.5-fold increase vs sham-castrated mice) and testosterone replacement reversed the castration-induced increase in metabolic BAT activity. BAT-specific AR deficiency did not mimic the castration effects in vivo and AR agonist treatment did not diminish the activity of cultured brown adipocytes in vitro, suggesting that androgens do not modulate BAT activity via a direct, AR-mediated pathway. In conclusion, testosterone is a negative regulator of metabolic BAT activity in male mice. Our findings provide new insight into the metabolic actions of testosterone.

 

  • Collapse
  • Expand
  • Bal NC, Singh S, Reis FCG, Maurya SK, Pani S, Rowland LA & Periasamy M 2017 Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice. Journal of Biological Chemistry 292 1661616625. (https://doi.org/10.1074/jbc.M117.790451)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H & Waurisch C et al.2011 Brown adipose tissue activity controls triglyceride clearance. Nature Medicine 17 200205. (https://doi.org/10.1038/nm.2297)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Basu D & Bornfeldt KE 2020 Hypertriglyceridemia and atherosclerosis: using human research to guide mechanistic studies in animal models. Frontiers in Endocrinology 11 504. (https://doi.org/10.3389/fendo.2020.00504)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Becher T, Palanisamy S, Kramer DJ, Eljalby M, Marx SJ, Wibmer AG, Butler SD, Jiang CS, Vaughan R & Schoder H et al.2021 Brown adipose tissue is associated with cardiometabolic health. Nature Medicine 27 5865. (https://doi.org/10.1038/s41591-020-1126-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Blaszkiewicz M, Willows JW, Johnson CP & Townsend KL 2019 The importance of peripheral nerves in adipose tissue for the regulation of energy balance. Biology 8 10. (https://doi.org/10.3390/biology8010010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cannon B & Nedergaard J 2004 Brown adipose tissue: function and physiological significance. Physiological Reviews 84 277359. (https://doi.org/10.1152/physrev.00015.2003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carpentier AC, Blondin DP, Virtanen KA, Richard D, Haman F & Turcotte ÉE 2018 Brown adipose tissue energy metabolism in humans. Frontiers in Endocrinology 9 447. (https://doi.org/10.3389/fendo.2018.00447)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cintron-Colon R, Shankar K, Sanchez-Alavez M & Conti B 2019 Gonadal hormones influence core body temperature during calorie restriction. Temperature 6 158168. (https://doi.org/10.1080/23328940.2019.1607653)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, Devos A, Tan K, Atanassova N, Claessens F & Lecureuil C et al.2004 A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. PNAS 101 13271332. (https://doi.org/10.1073/pnas.0308114100)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dibner MD & Black IB 1976 Elevation of sympathetic ganglion tyrosine hydroxylase activity in neonatal and adult rats by testosterone treatment. Journal of Neurochemistry 27 323324. (https://doi.org/10.1111/j.1471-4159.1976.tb01591.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dinas PC, Nikaki A, Jamurtas AZ, Prassopoulos V, Efthymiadou R, Koutedakis Y, Georgoulias P & Flouris AD 2015 Association between habitual physical activity and brown adipose tissue activity in individuals undergoing PET-CT scan. Clinical Endocrinology 82 147154. (https://doi.org/10.1111/cen.12620)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ermis N, Deniz F, Kepez A, Kara B, Azal O & Kutlu M 2010 Heart rate variability of young men with idiopathic hypogonadotropic hypogonadism. Autonomic Neuroscience: Basic and Clinical 152 8487. (https://doi.org/10.1016/j.autneu.2009.08.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fan W, Yanase T, Nomura M, Okabe T, Goto K, Sato T, Kawano H, Kato S & Nawata H 2005 Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes 54 10001008. (https://doi.org/10.2337/diabetes.54.4.1000)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fletcher LA, Kim K, Leitner BP, Cassimatis TM, O’Mara AE, Johnson JW, Halprin MS, McGehee SM, Brychta RJ & Cypess AM et al.2020 Sexual dimorphisms in adult human brown adipose tissue. Obesity 28 241246. (https://doi.org/10.1002/oby.22698)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Freedman RR 2014 Menopausal hot flashes: mechanisms, endocrinology, treatment. Journal of Steroid Biochemistry and Molecular Biology 142 115120. (https://doi.org/10.1016/j.jsbmb.2013.08.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fuller-Jackson JP, Dordevic AL, Clarke IJ & Henry BA 2020 Effect of sex and sex steroids on brown adipose tissue heat production in humans. European Journal of Endocrinology 183 343355. (https://doi.org/10.1530/EJE-20-0184)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gonzalez BD, Small BJ, Cases MG, Williams NL, Fishman MN, Jacobsen PB & Jim HSL 2018 Sleep disturbance in men receiving androgen deprivation therapy for prostate cancer: the role of hot flashes and nocturia. Cancer 124 499506. (https://doi.org/10.1002/cncr.31024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hashimoto O, Noda T, Morita A, Morita M, Ohtsuki H, Sugiyama M & Funaba M 2016 Castration induced browning in subcutaneous white adipose tissue in male mice. Biochemical and Biophysical Research Communications 478 17461750. (https://doi.org/10.1016/j.bbrc.2016.09.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hoeke G, Kooijman S, Boon MR, Rensen PC & Berbée JF 2016 Role of brown fat in lipoprotein metabolism and atherosclerosis. Circulation Research 118 173182. (https://doi.org/10.1161/CIRCRESAHA.115.306647)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jiao Q, Pruznak AM, Huber D, Vary TC & Lang CH 2009 Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue. American Journal of Physiology: Endocrinology and Metabolism 297 E1222E1232. (https://doi.org/10.1152/ajpendo.00473.2009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jones JM, Kohli M & Loprinzi CL 2012 Androgen deprivation therapy-associated vasomotor symptoms. Asian Journal of Andrology 14 193197. (https://doi.org/10.1038/aja.2011.101)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kahn BE & Brannigan RE 2017 Obesity and male infertility. Current Opinion in Urology 27 441445. (https://doi.org/10.1097/MOU.0000000000000417)

  • Kang S, Kong X & Rosen ED 2014 Adipocyte-specific transgenic and knockout models. Methods in Enzymology 537 116. (https://doi.org/10.1016/B978-0-12-411619-1.00001-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Keast JR 2000 Effects of testosterone on pelvic autonomic pathways: progress and pitfalls. Journal of the Autonomic Nervous System 79 6773. (https://doi.org/10.1016/s0165-1838(9900087-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kooijman S, van den Heuvel JK & Rensen PCN 2015 Neuronal control of brown fat activity. Trends in Endocrinology and Metabolism 26 657668. (https://doi.org/10.1016/j.tem.2015.09.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kroon J, Koorneef LL, van den Heuvel JK, Verzijl CRC, van de Velde NM, Mol IM, Sips HCM, Hunt H, Rensen PCN & Meijer OC 2018 Selective glucocorticoid receptor antagonist CORT125281 activates brown adipose tissue and alters lipid distribution in male mice. Endocrinology 159 535546. (https://doi.org/10.1210/en.2017-00512)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu J, Kuipers EN, Sips HCM, Dorleijn JC, van Dam AD, Christodoulides C, Karpe F, Zhou G, Boon MR & Rensen PCN et al.2019 Conditionally immortalized brown preadipocytes can switch between proliferative and differentiated states. Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids 1864 158511. (https://doi.org/10.1016/j.bbalip.2019.08.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lofgren L, Forsberg GB & Stahlman M 2016 The bume method: a new rapid and simple chloroform-free method for total lipid extraction of animal tissue. Scientific Reports 6 27688. (https://doi.org/10.1038/srep27688)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Monjo M, Rodriguez AM, Palou A & Roca P 2003 Direct effects of testosterone, 17 beta-estradiol, and progesterone on adrenergic regulation in cultured brown adipocytes: potential mechanism for gender-dependent thermogenesis. Endocrinology 144 49234930. (https://doi.org/10.1210/en.2003-0537)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Morrison SF 2016 Central control of body temperature. F1000 Research 5 880.(https://doi.org/10.12688/f1000research.7958.1)

  • Movérare-Skrtic S, Venken K, Andersson N, Lindberg MK, Svensson J, Swanson C, Vanderschueren D, Oscarsson J, Gustafsson JA & Ohlsson C 2006 Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice. Obesity 14 662672. (https://doi.org/10.1038/oby.2006.75)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Murphy RC, James PF, McAnoy AM, Krank J, Duchoslav E & Barkley RM 2007 Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry. Analytical Biochemistry 366 5970. (https://doi.org/10.1016/j.ab.2007.03.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nakamura Y & Nakamura K 2018 Central regulation of brown adipose tissue thermogenesis and energy homeostasis dependent on food availability. Pflugers Archiv 470 823837. (https://doi.org/10.1007/s00424-017-2090-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nilsson ME, Vandenput L, Tivesten Å, Norlen AK, Lagerquist MK, Windahl SH, Borjesson AE, Farman HH, Poutanen M & Benrick A et al.2015 Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry. Endocrinology 156 24922502. (https://doi.org/10.1210/en.2014-1890)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC & Richard D 2011 Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. Journal of Clinical Endocrinology and Metabolism 96 192199. (https://doi.org/10.1210/jc.2010-0989)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, Turcotte EE, Richard D & Carpentier AC 2012 Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. Journal of Clinical Investigation 122 545552. (https://doi.org/10.1172/JCI60433)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Periasamy M, Herrera JL & Reis FCG 2017 Skeletal muscle thermogenesis and its role in whole body energy metabolism. Diabetes and Metabolism Journal 41 327336. (https://doi.org/10.4093/dmj.2017.41.5.327)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, Reimold M, Häring HU, Claussen CD & Stefan N 2010 Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 59 1789–1793. (https://doi.org/10.2337/db10-0004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rensen PC, van Dijk MC, Havenaar EC, Bijsterbosch MK, Kruijt JK & van Berkel TJ 1995 Selective liver targeting of antivirals by recombinant chylomicrons: a new therapeutic approach to hepatitis B. Nature Medicine 1 221225. (https://doi.org/10.1038/nm0395-221)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodriguez AM, Monjo M, Roca P & Palou A 2002 Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cellular and Molecular Life Sciences 59 17141723. (https://doi.org/10.1007/pl00012499)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodriguez-Cuenca S, Pujol E, Justo R, Frontera M, Oliver J, Gianotti M & Roca P 2002 Sex-dependent thermogenesis, differences in mitochondrial morphology and function, and adrenergic response in brown adipose tissue. Journal of Biological Chemistry 277 4295842963. (https://doi.org/10.1074/jbc.M207229200)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodriguez-Cuenca S, Monjo M, Gianotti M, Proenza AM & Roca P 2007a Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17beta-estradiol, testosterone, and progesterone. American Journal of Physiology: Endocrinology and Metabolism 292 E340E346. (https://doi.org/10.1152/ajpendo.00175.2006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodriguez-Cuenca S, Monjo M, Frontera M, Gianotti M, Proenza AM & Roca P 2007b Sex steroid receptor expression profile in brown adipose tissue. Effects of hormonal status. Cellular Physiology and Biochemistry 20 877886. (https://doi.org/10.1159/000110448)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sanchez-Alavez M, Alboni S & Conti B 2011 Sex- and age-specific differences in core body temperature of C57BL/6 mice. Age 33 8999. (https://doi.org/10.1007/s11357-010-9164-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schilperoort M, Hoeke G, Kooijman S & Rensen PC 2016 Relevance of lipid metabolism for brown fat visualization and quantification. Current Opinion in Lipidology 27 242248. (https://doi.org/10.1097/MOL.0000000000000296)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schilperoort M, van Dam AD, Hoeke G, Shabalina IG, Okolo A, Hanyaloglu AC, Dib LH, Mol IM, Caengprasath N & Chan YW et al.2018 The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. EMBO Molecular Medicine 10 e8047. (https://doi.org/10.15252/emmm.201708047)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Serra C, Sandor NL, Jang H, Lee D, Toraldo G, Guarneri T, Wong S, Zhang A, Guo W & Jasuja R et al.2013 The effects of testosterone deprivation and supplementation on proteasomal and autophagy activity in the skeletal muscle of the male mouse: differential effects on high-androgen responder and low-androgen responder muscle groups. Endocrinology 154 45944606. (https://doi.org/10.1210/en.2013-1004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takahashi A, Adachi S, Morita M, Tokumasu M, Natsume T, Suzuki T & Yamamoto T 2015 Post-transcriptional stabilization of Ucp1 mRNA protects mice from diet-induced obesity. Cell Reports 13 27562767. (https://doi.org/10.1016/j.celrep.2015.11.056)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Townsend KL & Tseng YH 2014 Brown fat fuel utilization and thermogenesis. Trends in Endocrinology and Metabolism 25 168177. (https://doi.org/10.1016/j.tem.2013.12.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Turpin SM, Nicholls HT, Willmes DM, Mourier A, Brodesser S, Wunderlich CM, Mauer J, Xu E, Hammerschmidt P & Bronneke HS et al.2014 Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metabolism 20 678686. (https://doi.org/10.1016/j.cmet.2014.08.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van den Berg R, Kooijman S, Noordam R, Ramkisoensing A, Abreu-Vieira G, Tambyrajah LL, Dijk W, Ruppert P, Mol IM & Kramar B et al.2018 A diurnal rhythm in brown adipose tissue causes rapid clearance and combustion of plasma lipids at wakening. Cell Reports 22 35213533. (https://doi.org/10.1016/j.celrep.2018.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, Jorgensen JA, Wu J & Mottaghy FM et al.2013 Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. Journal of Clinical Investigation 123 33953403. (https://doi.org/10.1172/JCI68993)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wernstedt I, Edgley A, Berndtsson A, Faldt J, Bergstrom G, Wallenius V & Jansson JO 2006 Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 291 R551R 557. (https://doi.org/10.1152/ajpregu.00514.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wright AS, Thomas LN, Douglas RC, Lazier CB & Rittmaster RS 1996 Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat. Journal of Clinical Investigation 98 25582563. (https://doi.org/10.1172/JCI119074)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yanase T, Fan W, Kyoya K, Min L, Takayanagi R, Kato S & Nawata H 2008 Androgens and metabolic syndrome: lessons from androgen receptor knock out (ARKO) mice. Journal of Steroid Biochemistry and Molecular Biology 109 254257. (https://doi.org/10.1016/j.jsbmb.2008.03.017)

    • PubMed
    • Search Google Scholar
    • Export Citation