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

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Inder WJ, Jang C, Obeyesekere VR, Alford FP

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

Clin Endocrinol (Oxf). 2010 Jul;73(1):126-32. doi: 10.1111/j.1365-2265.2009.03683.x. Epub 2009 Aug 4.

PubMed ID
19681914 [ View in PubMed
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Abstract

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.