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Regulation of IGF‐I signal pathways by androgen in skeletal muscle of glucocorticoid‐treated rats
Author(s) -
Yin HuiNan,
Chai JiaKe,
Yu YongMing,
Shen ChuanAn,
Wu YanQiu,
Yao YongMing,
Liu Hui,
Liang LiMing,
Tompkins Ronald G.,
Sheng ZhiYong
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a336-b
Subject(s) - endocrinology , medicine , skeletal muscle , muscle atrophy , glucocorticoid , testosterone (patch) , protein kinase b , anabolism , chemistry , androgen , phosphorylation , gastrocnemius muscle , biology , hormone , biochemistry
The mechanisms by which androgens reverse glucocorticoid‐induced muscle wasting are not known. Recent studies suggest that the anabolic effects of testosterone in muscle may be mediated by the IGF‐1 signal pathways. We therefore examined the effect of testosterone on IGF‐1 signal pathway activation in skeletal muscle of glucocorticoid‐treated rats. Forty female Sprague‐Dawley rats were randomly divided into four groups: control group, dexamethasone (DEX) group, testosterone (TES) group and TES+DEX group. Testosterone attenuated the loss of body and gastrocnemius muscle weight and the decrease of muscle fiber CSA caused by DEX. TES prevented the decrese of IGF‐1 expression induced by DEX in skeletal muscle but not in serum. TES prevented DEX‐induced dephosphorylation of Akt and p70S6K two downstream targets of IGF‐1 associated with protein synthesis. TES also increased phosphorylation of GSK‐3¦Â another downstream target of IGF‐1 in skeletal muscle. Total Akt, p70S6K and GSK‐3¦Â protein was not changed between groups. DEX increased the expression of two protein breakdown‐related ubiquitin E3‐ligases, MAFbx and MurF1 mRNA in skeletal muscle, but TES failed to change the expression of MAFbx and MurF1 mRNA in skeletal muscle of control rats and DEX‐treated rats. The results suggest that TES in part reverses muscle atrophy in rats induced by DEX and protein synthesis pathways downstream of IGF‐1 in skeletal muscle may be involved in its mechanism.