Effects of corticosterone on muscle mitochondria identifying different sensitivity to glucocorticoids in Lewis and Fischer rats.
Previous studies in rat have demonstrated decreased number of mitochondria and uncoupling of oxidative phosphorylation after administration of glucocorticoids but at supraphysiological doses and using synthetic glucocorticoids. To analyze the relationships between corticosterone levels (the natural glucocorticoid in rat) and muscle mitochondrial metabolism, Lewis and Fischer 344 rats were bilaterally adrenalectomized and implanted with different corticosterone pellets (0, 12, 50, 100, and 200 mg of corticosterone). Rats bearing a corticosterone pellet delivering corticosterone at concentrations in the range of chronic stress-induced levels presented a lower amount of functional muscle mitochondria with a decrease in cytochrome c oxidase and citrate synthase activities and a depletion of mitochondrial DNA. Moreover, a strain difference in tissue sensitivity to corticosterone was depicted both in end-organ sensitive to glucocorticoids (body, thymus, and adrenal weights) and in muscle mitochondrial metabolism (Lewis > Fischer). Interestingly, this strain difference was also observed in the absence of corticosterone, with a deleterious effect on muscle mitochondrial metabolism in Fischer rats, whereas no effects were observed in Lewis rats. We therefore postulate that corticosterone is necessary for muscle mitochondrial metabolism exerting its effects in Fischer rats with an inverted U curve, whereby too little (only Fischer) or too much (Fischer and Lewis) corticosterone is deleterious to muscle mitochondrial metabolism. In conclusion, we propose a general model of coordinate regulation of mitochondrial energetic metabolism by glucocorticoids.
Duclos
Martine
M
Laboratoire Neurogénétique et Stress, Institut National de la Santé et de la Recherche Médicale U471, Institut François Magendie, Université Bordeaux II, 33077 Bordeaux, France. duclos@pop.bordeaux.inserm.fr
Gouarne
Caroline
C
Martin
Cyril
C
Rocher
Christophe
C
Mormède
Pierre
P
Letellier
Thierry
T
D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004343:Drug Implants; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013950:Thymus Gland / Q000033:anatomy & histology
D004272:DNA, Mitochondrial; D004343:Drug Implants; D005938:Glucocorticoids; D011451:Prostaglandin-Endoperoxide Synthases; D013385:Succinate Dehydrogenase; D003345:Corticosterone