Endocrine Abstracts (2012) 28 P209

Expression and metabolic function of androgen receptor in mouse adipose tissue

James Turton1, Meritxell Rosell Mane1, Eleni Daniel1, Malcolm Parker1, Saverio Cinti2, Andrea Frontini2, Kate Hardy1, Stephen Franks1 & Mark Christian1

1Institute of Reproductive & Developmental Biology, Imperial College London, London, United Kingdom; 2Dept of Experimental and Clinical Medicine, Università Politecnica delle Marche (University of Ancona), Ancona, Italy.

Hyperandrogenism in women, most typically in polycystic ovary syndrome, is associated with insulin resistance and altered morphology and function of adipose tissue but little is known about the direct effects of androgen on adipose. The aims of this study were to investigate (1) distribution and relative abundance of androgen receptor (AR) in mouse adipose tissue (2) effect of temperature on AR expression in brown and white adipose depots (BAT, WAT) and (3) effects of androgen on gene expression and insulin signalling in adipocyte cell lines derived from BAT and WAT. A microarray study was performed on interscapular BAT, subcutaneous WAT and mesenteric WAT from Sv129 female mice (10 week old) maintained at 28° C (thermoneutral), or 6° C (cold) for 10 days. AR in BAT was more highly expressed at 28° compared to 6° C. q-RT-PCR analysis of adipose tissue depots showed that AR expression was greatest in periovarian WAT with lowest levels in interscapular BAT. In both interscapular BAT and subcutaneous WAT, levels of AR were reduced at 6° compared to mice maintained at thermoneutrality or 22° C. AR expression in the stromal vascular fraction (SVF) and mature adipocyte fraction from different depots were examined; AR levels were greater in the adipocyte fraction from gonadal WAT than in SVF. In contrast, AR levels were similar for SVF and adipocytes of interscapular BAT and subcutaneous WAT. In cultured adipocytes, exposure to dihydrotestosterone (DHT) resulted in a significant increase in the androgen-dependent genes Nr3c4, E112, Fkbp5 and Ndrg1 in both BAT and WAT (qPCR). Importantly, DHT (10nM) delayed and suppressed peak insulin-stimulated Akt phosphorylation in WAT and suppressed the response in BAT. In conclusion, these results indicate that AR is abundant in WAT, its expression is depot and temperature dependent, and androgen modifies insulin signaling in both WAT and BAT.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: MRC and Genesis Research Trust.

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