Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass
Journal of Endocrinology, vol. 264
Abstract
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.
Authors 11
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Vera Sommers Aachen Department of Internal Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine
Leiden University Medical Center · KU Leuven
Affiliation as printed
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
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
V Sommers, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
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Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
K David, Laboratory of Clinical and Experimental Endocrinology, Department Chronic diseases and metabolism, KU Leuven, Leuven, Belgium
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Affiliation as printed
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
C Helsen, Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
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Affiliation as printed
Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
K Moermans, Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
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Affiliation as printed
Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
I Stockmans, Chronic diseases and Metabolism, KU Leuven, Leuven, Belgium
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Affiliation as printed
Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
R Dmitriev, Tissue Engineering and Biomaterials Group, UGent, Gent, Belgium
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Affiliation as printed
Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
S Stegen, Clinical and Experimental Endocrinology - Department of Chronic diseases and Metabolism, KU Leuven, Leuven, 3000, Belgium
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Onno Cornelis Meijer Aachen Department of Internal Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine O Meijer
Leiden University Medical Center
Affiliation as printed
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
O Meijer, Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
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Jan Kroon Aachen Department of Internal Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine J Kroon
Leiden University Medical Center
Affiliation as printed
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
J Kroon, Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
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Affiliation as printed
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
F Claessens, Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
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Affiliation as printed
Laboratory of Basic and Translational Endocrinology, Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
V Dubois, Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
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