Premium
Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF‐1 – implications for steroid‐induced myopathy
Author(s) -
Inder Warrick J.,
Jang Christina,
Obeyesekere Varuni R.,
Alford Frank P.
Publication year - 2010
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2009.03683.x
Subject(s) - endocrinology , medicine , androgen receptor , androgen , testosterone (patch) , dexamethasone , glucocorticoid , glucocorticoid receptor , receptor , skeletal muscle , biology , hormone , prostate cancer , cancer
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.