Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass

in Journal of Endocrinology
Authors:
Vera Sommers Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands

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Karel David Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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Christine Helsen Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Karen Moermans Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium

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Ingrid Stockmans Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium

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Gabriele Ferrari Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Ruslan I Dmitriev Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Steve Stegen Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium

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Onno C Meijer Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands

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Jan Kroon Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands

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Frank Claessens Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Vanessa Dubois Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Laboratory of Basic and Translational Endocrinology, Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Correspondence should be addressed to V Dubois: vanessa.dubois@ugent.be

(O C Meijer, J Kroon, F Claessens and V Dubois contributed equally to this work)

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Glucocorticoids and androgens affect each other in several ways. In metabolic organs, such as adipose tissue and the liver, androgens enhance glucocorticoid-induced insulin resistance and promote fat accumulation in male mice. However, the direct contribution of the androgen receptor (AR) to these effects is unknown. Furthermore, it is unclear whether the potentiating effect of androgens on glucocorticoid signaling in fat extends to other tissues, such as skeletal muscle and bone. In this study, we used two complementary models for androgen deprivation (orchidectomy and chemical castration) to investigate the effects of dihydrotestosterone (DHT) on corticosterone (CORT). We found that after 2 weeks of intervention, DHT alone did not affect fat mass but increased lean mass, while CORT increased fat mass and decreased lean mass. Co-supplementation with DHT counteracted the CORT effect on lean mass but enhanced its effect on adiposity. Glucocorticoid induction of Gilz, Fkbp5 and Mt2a in gonadal white adipose tissue depended on the presence of androgens, while in interscapular brown adipose tissue, these genes responded to glucocorticoids also without androgens. To directly assess the impact of the AR on the glucocorticoid response, male global AR knock-out mice were exposed to CORT and compared to WT littermates. CORT exposure resulted in an increase in fat mass and a decrease in lean mass in both genotypes. In conclusion, functional AR signaling is dispensable for the metabolic response to glucocorticoids. However, androgen signaling in WT mice modulates glucocorticoid response in a tissue-dependent manner, by counteracting lean mass and potentiating fat mass effects.

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  • Arora VK, Schenkein E, Murali R, et al. 2013 Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155 13091322. (https://doi.org/10.1016/j.cell.2013.11.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Badraoui R, Amri N, Zammel N, et al. 2017 Corticosteroid treatment exacerbates bone osteopenia in mice with gonadal hormone deficiency-induced osteoporosis. Eur J Pharm Sci 105 4146. (https://doi.org/10.1016/j.ejps.2017.04.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bodine SC & Furlow JD 2015 Glucocorticoids and skeletal muscle. Adv Exp Med Biol 872 145176. (https://doi.org/10.1007/978-1-4939-2895-8_7)

  • Buurstede JC, Paul SN, De Bosscher K, et al. 2022 Hepatic glucocorticoid-induced transcriptional regulation is androgen-dependent after chronic but not acute glucocorticoid exposure. FASEB J 36 e22251. (https://doi.org/10.1096/fj.202101313r)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Canalis E & Delany AM 2002 Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci 966 7381. (https://doi.org/10.1111/j.1749-6632.2002.tb04204.x)

  • Chapman K, Holmes M & Seckl J 2013 11β-Hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 93 11391206. (https://doi.org/10.1152/physrev.00020.2012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen S, Wang J, Yu G, et al. 1997 Androgen and glucocorticoid receptor heterodimer formation. J Biol Chem 272 1408714092. (https://doi.org/10.1074/jbc.272.22.14087)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Coutinho AE, Gray M, Brownstein DG, et al. 2012 11β-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice. Endocrinology 153 234240. (https://doi.org/10.1210/en.2011-1398)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davies P & Rushmere NK 1990 Association of glucocorticoid receptors with prostate nuclear sites for androgen receptors and with androgen response elements. J Mol Endocrinol 5 117127. (https://doi.org/10.1677/jme.0.0050117)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Bosscher K, Desmet SJ, Clarisse D, et al. 2020 Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation. Nat Rev Endocrinol 16 363377. (https://doi.org/10.1038/s41574-020-0349-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Gendt K, Swinnen JV, Saunders PT, et al. 2004 A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci U S A 101 13271332. (https://doi.org/10.1073/pnas.0308114100)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Naeyer H, Lamon S, Russell AP, et al. 2014 Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice. Eur J Appl Physiol 114 751761. (https://doi.org/10.1007/s00421-013-2800-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dempster DW, Compston JE, Drezner MK, et al. 2013 Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28 217. (https://doi.org/10.1002/jbmr.1805)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dieudonné MN, Sammari A, Dos Santos E, et al. 2006 Sex steroids and leptin regulate 11β-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: sex specificities. J Steroid Biochem Mol Biol 99 189196. (https://doi.org/10.1016/j.jsbmb.2006.01.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Doig CL, Fletcher RS, Morgan SA, et al. 2017 11β-HSD1 modulates the set point of brown adipose tissue response to glucocorticoids in male mice. Endocrinology 158 19641976. (https://doi.org/10.1210/en.2016-1722)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dubois V, Laurent M, Boonen S, et al. 2012 Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions. Cell Mol Life Sci 69 16511667. (https://doi.org/10.1007/s00018-011-0883-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dubois V, Laurent MR, Sinnesael M, et al. 2014 A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle. FASEB J 28 29792994. (https://doi.org/10.1096/fj.14-249748)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dubois V, Simitsidellis I, Laurent MR, et al. 2015 Enobosarm (GTx-024) modulates adult skeletal muscle mass independently of the androgen receptor in the satellite cell lineage. Endocrinology 156 45224533. (https://doi.org/10.1210/en.2015-1479)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dubois V, Laurent MR, Jardi F, et al. 2016 Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice. Endocrinology 157 648665. (https://doi.org/10.1210/en.2015-1713)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Duma D, Collins JB, Chou JW, et al. 2010 Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence. Sci Signal 3 ra74. (https://doi.org/10.1126/scisignal.2001077)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gasparini SJ, Swarbrick MM, Kim S, et al. 2019 Androgens sensitise mice to glucocorticoid-induced insulin resistance and fat accumulation. Diabetologia 62 14631477. (https://doi.org/10.1007/s00125-019-4887-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gennari L, Nuti R & Bilezikian JP 2004 Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab 89 58985907. (https://doi.org/10.1210/jc.2004-1717)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gomez-Sanchez E & Gomez-Sanchez CE 2014 The multifaceted mineralocorticoid receptor. Compr Physiol 4 965994. (https://doi.org/10.1002/cphy.c130044)

  • Hardy RS, Zhou H, Seibel MJ, et al. 2018 Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy. Endocr Rev 39 519548. (https://doi.org/10.1210/er.2018-00097)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hua C, Buttgereit F & Combe B 2020 Glucocorticoids in rheumatoid arthritis: current status and future studies. RMD Open 6 e000536. (https://doi.org/10.1136/rmdopen-2017-000536)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huan C, Qu Y & Ren Z 2014 Gender differences in presentation and outcome of patients with Cushing’s disease in Han Chinese. Biomed Mater Eng 24 34393446. (https://doi.org/10.3233/bme-141168)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ipulan LA, Suzuki K, Sakamoto Y, et al. 2014 Nonmyocytic androgen receptor regulates the sexually dimorphic development of the embryonic bulbocavernosus muscle. Endocrinology 155 24672479. (https://doi.org/10.1210/en.2014-1008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kadmiel M & Cidlowski JA 2013 Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 34 518530. (https://doi.org/10.1016/j.tips.2013.07.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kaikaew K, Steenbergen J, Van Dijk TH, et al. 2019 Sex difference in corticosterone-induced insulin resistance in mice. Endocrinology 160 23672387. (https://doi.org/10.1210/en.2019-00194)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Khalil R, Simitsidellis I, Kim NR, et al. 2020 Androgen action on renal calcium and phosphate handling: effects of bisphosphonate treatment and low calcium diet. Mol Cell Endocrinol 514 110891. (https://doi.org/10.1016/j.mce.2020.110891)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim NR, Jardí F, Khalil R, et al. 2020 Estrogen receptor alpha signaling in extrahypothalamic neurons during late puberty decreases bone size and strength in female but not in male mice. FASEB J 34 71187126. (https://doi.org/10.1096/fj.202000272r)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim NR, David K, Corbeels K, et al. 2021a Testosterone reduces body fat in male mice by stimulation of physical activity via extrahypothalamic ERα signaling. Endocrinology 162 bqab045. (https://doi.org/10.1210/endocr/bqab045)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim NR, Khalil R, David K, et al. 2021b Novel model to study the physiological effects of temporary or prolonged sex steroid deficiency in male mice. Am J Physiol Endocrinol Metab 320 E415e424. (https://doi.org/10.1152/ajpendo.00401.2020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Koorneef LL, Kroon J, Viho EMG, et al. 2020 The selective glucocorticoid receptor antagonist CORT125281 has tissue-specific activity. J Endocrinol 246 7992. (https://doi.org/10.1530/joe-19-0486)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kroon J, Pereira AM & Meijer OC 2020 Glucocorticoid sexual dimorphism in metabolism: dissecting the role of sex hormones. Trends Endocrinol Metab 31 357367. (https://doi.org/10.1016/j.tem.2020.01.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kulik M, Bothe M, Kibar G, et al. 2021 Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites. Nucleic Acids Res 49 38563875. (https://doi.org/10.1093/nar/gkab185)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kuo T-R & Chen C-H 2017 Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomark Res 5 18. (https://doi.org/10.1186/s40364-017-0097-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li T, Yan F, Meng X, et al. 2018 Improvement of glucocorticoid-impaired thymus function by dihydromyricetin via up-regulation of PPARγ-associated fatty acid metabolism. Pharmacol Res 137 7688. (https://doi.org/10.1016/j.phrs.2018.09.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li S, Schönke M, Buurstede JC, et al. 2022 Sexual dimorphism in transcriptional and functional glucocorticoid effects on mouse skeletal muscle. Front Endocrinol 13 907908. (https://doi.org/10.3389/fendo.2022.907908)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Martín AI, Priego T & López-Calderón A 2018 Hormones and muscle atrophy. Adv Exp Med Biol 1088 207233. (https://doi.org/10.1007/978-981-13-1435-3_9)

  • Okita K, Iwahashi H, Kozawa J, et al. 2013 Homeostasis model assessment of insulin resistance for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy. Endocr J 60 283290. (https://doi.org/10.1507/endocrj.ej12-0320)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Paakinaho V & Palvimo JJ 2021 Genome-wide crosstalk between steroid receptors in breast and prostate cancers. Endocr Relat Cancer 28 R231R250. (https://doi.org/10.1530/erc-21-0038)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pecori Giraldi F, Moro M & Cavagnini F 2003 Gender-related differences in the presentation and course of Cushing’s disease. J Clin Endocrinol Metab 88 15541558. (https://doi.org/10.1210/jc.2002-021518)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Perilli E, Cantley M, Marino V, et al. 2015 Quantifying not only bone loss, but also soft tissue swelling, in a murine inflammatory arthritis model using micro-computed tomography. Scand J Immunol 81 142150. (https://doi.org/10.1111/sji.12259)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Poetker DM & Reh DD 2010 A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am 43 753768. (https://doi.org/10.1016/j.otc.2010.04.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Præstholm SM, Correia CM & Grøntved L 2020 Multifaceted control of GR signaling and its impact on hepatic transcriptional networks and metabolism. Front Endocrinol 11 572981. (https://doi.org/10.3389/fendo.2020.572981)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Quinn M, Ramamoorthy S & Cidlowski JA 2014 Sexually dimorphic actions of glucocorticoids: beyond chromosomes and sex hormones. Ann N Y Acad Sci 1317 16. (https://doi.org/10.1111/nyas.12425)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rand MN & Breedlove SM 1992 Androgen locally regulates rat bulbocavernosus and levator ani size. J Neurobiol 23 1730. (https://doi.org/10.1002/neu.480230104)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sahu B, Laakso M, Pihlajamaa P, et al. 2013 FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res 73 15701580. (https://doi.org/10.1158/0008-5472.can-12-2350)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sahu B, Pihlajamaa P, Dubois V, et al. 2014 Androgen receptor uses relaxed response element stringency for selective chromatin binding and transcriptional regulation in vivo. Nucleic Acids Res 42 42304240. (https://doi.org/10.1093/nar/gkt1401)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Savas M, Muka T, Wester VL, et al. 2017 Associations between systemic and local corticosteroid use with metabolic syndrome and body mass index. J Clin Endocrinol Metab 102 37653774. (https://doi.org/10.1210/jc.2017-01133)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sebo ZL & Rodeheffer MS 2021 Testosterone metabolites differentially regulate obesogenesis and fat distribution. Mol Metab 44 101141. (https://doi.org/10.1016/j.molmet.2020.101141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shimizu N, Yoshikawa N, Ito N, et al. 2011 Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab 13 170182. (https://doi.org/10.1016/j.cmet.2011.01.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Spaanderman DCE, Nixon M, Buurstede JC, et al. 2018 Androgens modulate glucocorticoid receptor activity in adipose tissue and liver. J Endocrinol 240 5163. (https://doi.org/10.1530/JOE-18-0503)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stegen S, Moermans K, Stockmans I, et al. 2024 The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression. Nat Metab 6 141152. (https://doi.org/10.1038/s42255-023-00948-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Valassi E, Santos A, Yaneva M, et al. 2011 The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol 165 383392. (https://doi.org/10.1530/eje-11-0272)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Van Den Beukel JC, Boon MR, Steenbergen J, et al. 2015 Cold exposure partially corrects disturbances in lipid metabolism in a male mouse model of glucocorticoid excess. Endocrinology 156 41154128. (https://doi.org/10.1210/en.2015-1092)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vandenput L, Boonen S, Van Herck E, et al. 2002 Evidence from the aged orchidectomized male rat model that 17β-estradiol is a more effective bone-sparing and anabolic agent than 5α-dihydrotestosterone. J Bone Miner Res 17 20802086. (https://doi.org/10.1359/jbmr.2002.17.11.2080)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vandevyver S, Dejager L & Libert C 2014 Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 35 671693. (https://doi.org/10.1210/er.2014-1010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Viau V, Chu A, Soriano L, et al. 1999 Independent and overlapping effects of corticosterone and testosterone on corticotropin-releasing hormone and arginine vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus and stress-induced adrenocorticotropic hormone release. J Neurosci 19 66846693. (https://doi.org/10.1523/jneurosci.19-15-06684.1999)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walker BR & Andrew R 2006 Tissue production of cortisol by 11β‐hydroxysteroid dehydrogenase type 1 and metabolic disease. Ann N Y Acad Sci 1083 165184. (https://doi.org/10.1196/annals.1367.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang Y & Pessin JE 2013 Mechanisms for fiber-type specificity of skeletal muscle atrophy. Curr Opin Clin Nutr Metab Care 16 243250. (https://doi.org/10.1097/mco.0b013e328360272d)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang C, Nanni L, Novakovic B, et al. 2019 Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages. Sci Rep 9 2772. (https://doi.org/10.1038/s41598-019-39395-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Weinstein RS, Jia D, Powers CC, et al. 2004 The skeletal effects of glucocorticoid excess override those of orchidectomy in mice. Endocrinology 145 19801987. (https://doi.org/10.1210/en.2003-1133)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wendowski O, Redshaw Z & Mutungi G 2017 Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres. J Cachexia Sarcopenia Muscle 8 4856. (https://doi.org/10.1002/jcsm.12122)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Whittier DE, Boyd SK, Burghardt AJ, et al. 2020 Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int 31 16071627. (https://doi.org/10.1007/s00198-020-05438-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wilhelmson AS, Lantero Rodriguez M, Svedlund Eriksson E, et al. 2018 Testosterone protects against atherosclerosis in male mice by targeting thymic epithelial cells-brief report. Arterioscler Thromb Vasc Biol 38 15191527. (https://doi.org/10.1161/atvbaha.118.311252)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wood CL, Soucek O, Wong SC, et al. 2018 Animal models to explore the effects of glucocorticoids on skeletal growth and structure. J Endocrinol 236 R69r91. (https://doi.org/10.1530/joe-17-0361)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu H & Ballantyne CM 2020 Metabolic inflammation and insulin resistance in obesity. Circ Res 126 15491564. (https://doi.org/10.1161/circresaha.119.315896)

  • Zhao W, Pan J, Zhao Z, et al. 2008 Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol 110 125129. (https://doi.org/10.1016/j.jsbmb.2008.03.024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhu L, Hou M, Sun B, et al. 2010 Testosterone stimulates adipose tissue 11β-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children. J Clin Endocrinol Metab 95 33003308. (https://doi.org/10.1210/jc.2009-2708)

    • PubMed
    • Search Google Scholar
    • Export Citation