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Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 – implications for steroid-induced myopathy

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Summary Context 

Glucocorticoids are a well-recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF-1 pathways have not been previously investigated in human subjects. Objective 

To determine if administration of the potent glucocorticoid dexamethasone down-regulates SkM androgen receptor and the IGF-1 signalling pathway. Methods and subjects 

Twenty-four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days. Main outcome measures 

Changes in plasma testosterone and IGF-1, SkM androgen receptor mRNA, SkM IGF-1mRNA and SkM IGF-1 receptor mRNA by quantitative RT-PCR after dexamethasone. Results 

Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF-1 and SkM expression of IGF-1 and IGF-1 receptor were also similar between males and females. Following dexamethasone, there was a significant down-regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P <0·05) and IGF-1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P <0·05) mRNA, but no change in expression of the IGF-1 receptor. Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P <0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P <0·05). Conclusions 

Exogenous steroid excess results in relative androgen deficiency at two levels, reduced circulating testosterone and SkM androgen receptor mRNA, along with reduced SkM IGF-1 mRNA. These defects may contribute to the development of steroid-induced myopathy.
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Document Type: Research Article

Affiliations: Department of Endocrinology, St Vincent’s Hospital, Melbourne

Publication date: July 1, 2010

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