Epidemiological evidence suggests alcoholic
myopathy is more severe in females than males, but comparable animal studies are lacking that make elucidating the biochemical locus for this defect problematic. The present study determined whether skeletal muscle
protein synthesis and markers of degradation exhibit a sexual dimorphic response to either chronic alcohol consumption or acute intoxication. Male and female rats were fed an alcohol-containing diet, pair-fed for 26 wk (chronic), or received an
intraperitoneal injection of alcohol (acute). In males, chronic alcohol decreased gastrocnemius
protein synthesis by 20%. This reduction was associated with a twofold increase in the inactive eukaryotic
initiation factor (eIF) 4E.4E-binding
protein 1 (4E-BP1) complex and a 60% reduction in the active
eIF4E.
eIF4G complex. This redistribution of
eIF4E was associated with decreased phosphorylation of both 4E-BP1 and
eIF4G (50-55%). The phosphorylation of
ribosomal protein S6 was also reduced 60% in alcohol-consuming male rats. In contrast, neither rates of
protein synthesis nor indexes of translation initiation in muscle were altered in alcohol-fed female rats despite blood alcohol levels comparable to males. Chronic alcohol ingestion did not alter atrogin-1 or muscle RING finger-1
mRNA content (
biomarkers of muscle proteolysis) in males but increased their expression in females 50-100%. Acute alcohol intoxication produced a comparable decrease in
muscle protein synthesis and translation initiation in both male and female rats. Our data demonstrate a sexual dimorphism for
muscle protein synthesis, translation initiation, and proteolysis in response to chronic, but not acute, alcohol intoxication; however, they do not support evidence indicating females are more sensitive toward the development of alcoholic skeletal muscle
myopathy.