Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats.
This experiment was undertaken to examine leucine responsiveness of muscle protein synthesis during dexamethasone treatment and the subsequent recovery in young (4-5 weeks), adult (10-11 months) and old rats (21-22 months). Rats received dexamethasone in their drinking water. The dose and length of the treatment was adapted in order to generate the same muscle atrophy. Protein synthesis was assessed in vitro by incorporation of radiolabelled phenylalanine into proteins at the end of the treatment and after 3 or 7-day recovery. Results showed that dexamethasone did not alter muscle protein synthesis stimulation by leucine in young rats. In contrast, muscles from adult and old rats became totally resistant to leucine. Furthermore, the recovery of leucine responsiveness after dexamethasone withdrawal was slowed down in old rats when compared to younger rats. We concluded that glucocorticoids exert their catabolic action in adult and old rats partly through antagonising the stimulatory effect of leucine and may contribute to sarcopenia in old rats.
Unité de Nutrition et Métabolisme Protéique, Human Nutrition Research Centre of Clermont-Ferrand, Institut National de la Recherche Agronomique, Saint Genes Champanelle, 63122 Ceyrat, France. irieu@sancy.clermont.inra.fr
Isabelle
I
Rieu
Claire
C
Sornet
Jean
J
Grizard
Dominique
D
Dardevet
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004435:Eating / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007930:Leucine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
D005938:Glucocorticoids; D009124:Muscle Proteins; D003907:Dexamethasone; D007930:Leucine