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Androgens modulate glucocorticoid receptor activity in adipose 1 tissue and liver

Lookup NU author(s): Professor Brian Walker

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by BioScientifica Ltd, 2019.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

Glucocorticoid signaling is context-dependent, and in certain scenarios glucocorticoid receptors (GR) are able to engage with other members of the nuclear receptor subfamily. Glucocorticoid signaling can exert sexually dimorphic effects, suggesting a possible interaction with androgen sex hormones. We therefore set out to determine the crosstalk between glucocorticoids and androgens in metabolic tissues including white adipose tissue, liver and brown adipose tissue. Thereto we exposed male C57BL/6J mice to elevated levels of corticosterone in combination with an androgen receptor (AR) agonist or an AR antagonist. Systemic and local glucocorticoid levels were determined by mass spectrometry, tissue expression of glucocorticoid-responsive genes and protein was measured by RT-qPCR and Western blot, respectively. To evaluate crosstalk in vitro, cultured white and brown adipocytes were exposed to a combination of corticosterone and an androgen agonist. We found that AR agonism potentiated transcriptional response to GR in vitro in white and brown adipocytes and in vivo in white and brown adipose tissue. Conversely, AR antagonism substantially attenuated glucocorticoid signaling in white adipose tissue and liver. In white adipose tissue this effect could partially be attributed to decreased 11B-hydroxysteroid dehydrogenase type 1-mediated glucocorticoid regeneration upon AR antagonism. In liver, attenuated GR activity was independent of active glucocorticoid ligand levels. We conclude that androgen signaling modulates GR transcriptional output in a tissue-specific manner.


Publication metadata

Author(s): Spaanderman DCE, Nixon M, Buurstede JC, Sips HHCM, Schilperoort M, Kuipers EN, Backer EA, Kooijman S, Rensen PCN, Homer NZM, Walker BR, Meijer OC, Kroon J

Publication type: Article

Publication status: Published

Journal: Journal of Endocrinology

Year: 2019

Volume: 240

Issue: 1

Pages: 51-63

Online publication date: 04/10/2018

Acceptance date: 04/10/2018

Date deposited: 04/10/2018

ISSN (print): 0022-0795

ISSN (electronic): 1479-6805

Publisher: BioScientifica Ltd

URL: https://doi.org/10.1530/JOE-18-0503

DOI: 10.1530/JOE-18-0503


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