Myocyte Androgen Receptors Increase Metabolic Rate and Improve Body Composition by Reducing Fat Mass

Fernando, Shannon M.; Rao, Pengcheng; Niel, Lee; Chatterjee, Diptendu; Stagljar, Marijana; Monks, D. Ashley

doi:10.1210/en.2010-0018

Cited by 59 publications

(67 citation statements)

References 32 publications

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“…HMOX1 is a key enzyme in the breakdown of heme (Platt and Nath, 1998), and has been implicated in the disruption of human glucose regulation (Bao et al, 2012). Therefore, HMOX1's lower expression in testosterone-treated males is consistent with previous findings that testosterone increases metabolism (Oppliger et al, 2004;Fernando et al, 2010), as well as other studies that have linked heme-related enzymes with activational effects of androgens (van Nas et al, 2009). Aldehyde oxidase 1 (AOX1) was also expressed at lower levels in the liver of testosterone-treated males than controls.…”

Section: Effect Of Testosterone Treatment In Malessupporting

confidence: 89%

“…We also identified 291 genes that showed significantly different expression between control males and control females in the liver, and several of the differentially expressed genes were related to known phenotypic differences between the sexes. For example, Lipid phosphate phosphohydrolase 1, a gene involved in glycerolipid synthesis and lipid uptake (Kai et al, 1997), was expressed at a higher level in control males than females, consistent with sex differences in metabolic activity (Fernando et al, 2010;Wikelski et al, 1999). Further, the GO term steroid binding was over-represented among these genes.…”

Section: Sexually Dimorphic Gene Expressionmentioning

confidence: 80%

“…Similarly, muscle tissues are also often sensitive to testosterone and play a primary role in mediating dimorphic behavior and physiology (Arnold et al, 1997;Baur et al, 2008;Fernando et al, 2010). Gene expression appears to account for many sexually dimorphic muscle features in humans (Maher et al, 2009;Welle et al, 2008) and mice (Yang et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird

Peterson

Rosvall

Taylor

et al. 2013

Journal of Experimental Biology

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Males and females can be highly dimorphic in metabolism and physiology despite sharing nearly identical genomes, and both sexes respond phenotypically to elevated testosterone, a steroid hormone that alters gene expression. Only recently has it become possible to learn how a hormone such as testosterone affects global gene expression in non-model systems, and whether it affects the same genes in males and females. To investigate the transcriptional mechanisms by which testosterone exerts its metabolic and physiological effects on the periphery, we compared gene expression by sex and in response to experimentally elevated testosterone in a well-studied bird species, the dark-eyed junco (Junco hyemalis). We identified 291 genes in the liver and 658 in the pectoralis muscle that were differentially expressed between males and females. In addition, we identified 1727 genes that were differentially expressed between testosterone-treated and control individuals in at least one tissue and sex. Testosterone treatment altered the expression of only 128 genes in both males and females in the same tissue, and 847 genes were affected significantly differently by testosterone treatment in the two sexes. These substantial differences in transcriptional response to testosterone suggest that males and females may employ different pathways when responding to elevated testosterone, despite the fact that many phenotypic effects of experimentally elevated testosterone are similar in both sexes. In contrast, of the 121 genes that were affected by testosterone treatment in both sexes, 78% were regulated in the same direction (e.g. either higher or lower in testosteronetreated than control individuals) in both males and females. Thus, it appears that testosterone acts through both unique and shared transcriptional pathways in males and females, suggesting multiple mechanisms by which sexual conflict can be mediated.

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Section: Effect Of Testosterone Treatment In Malessupporting

confidence: 89%

Section: Sexually Dimorphic Gene Expressionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird

Peterson

Rosvall

Taylor

et al. 2013

Journal of Experimental Biology

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“…In rodent models, there is evidence that testosterone may increase the metabolic rate via androgen receptor-dependent actions on skeletal muscle (Fernando et al 2010). Mice lacking the androgen receptor have decreased physical activity, which may, at least in part, be responsible for their sarcopaenic obesity (Rana et al 2011).…”

Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 99%

Testosterone and glucose metabolism in men: current concepts and controversies

Grossmann¹

2013

Journal of Endocrinology

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A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic-pituitary-testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

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“…Genetic manipulation of mice and rats indicates a modest role for AR in myocytes in promoting muscle mass in some fibre types, and more robust effects of AR in myocytes in regulating energy production and storage in skeletal muscle and energy balance systemically, including loss of fat mass (e.g. [16]). Consistent with an evolutionary constraint on AR action on muscle, sufficient overexpression of AR in myocytes is associated with perinatal male mortality and neuromuscular atrophy [13] and also loss of fat mass [16], which remains an important energy source in AGS.…”

Section: Discussionmentioning

confidence: 99%

Managing anabolic steroids in pre-hibernating Arctic ground squirrels: obtaining their benefits and avoiding their costs

Boonstra

Monks

2014

Biol. Lett.

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Androgens have benefits, such as promoting muscle growth, but also significant costs, including suppression of immune function. In many species, these tradeoffs in androgen action are reflected in regulated androgen production, which is typically highest only in reproductive males. However, all non-reproductive Arctic ground squirrels, irrespective of age and sex, have high levels of androgens prior to hibernating at sub-zero temperatures. Androgens appear to be required to make muscle in summer, which, together with lipid, is then catabolized during overwinter. By contrast, most hibernating mammals catabolize only lipid. We tested the hypothesis that androgen action is selectively enhanced in Arctic ground squirrel muscle because of an upregulation of androgen receptors (ARs). Using Western blot analysis, we found that Arctic ground squirrels have AR in skeletal muscle more than four times that of Columbian ground squirrels, a related southern species that overwinters at approximately 08C and has low pre-hibernation androgen levels. By contrast, AR in lymph nodes was equivalent in both species. Brain AR was also modestly but significantly increased in Arctic ground squirrel relative to Columbian ground squirrel. These results are consistent with the hypothesis that tissue-specific AR regulation prior to hibernation provides a mechanism whereby Arctic ground squirrels obtain the life-history benefits and mitigate the costs associated with high androgen production.

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Myocyte Androgen Receptors Increase Metabolic Rate and Improve Body Composition by Reducing Fat Mass

Cited by 59 publications

References 32 publications

Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird

Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird

Testosterone and glucose metabolism in men: current concepts and controversies

Managing anabolic steroids in pre-hibernating Arctic ground squirrels: obtaining their benefits and avoiding their costs

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