Relative changes in the function of muscle ribosomes and mitochondria during the early phase of steroid-induced catabolism.

Abstract

1. Five glucocorticoids, when administered daily to rats for 5-7 days at a dosage of 5mg/kg, were in the following order of effectiveness with respect to their ability to decrease the weight gain of whole animals and the vastus lateralis, vastus medialis and gluteus medius muscles: corticosterone<prednisolone<triamcinolone <betamethasone<dexamethasone<triamcinolone acetonide. 2. The low catabolic potencies of corticosterone and prednisolone were reflected in the high doses (20mg/kg) required to decrease significantly the incorporating activity in vitro of ribosomes isolated from the muscles 6h later. However, triamcinolone was as effective as triamcinolone acetonide in causing a significant effect at 0.05mg/kg, although it had a far lower catabolic potency than the acetonide. 3. The relationship between decrease in ribosomal activity in vitro and weight loss was better understood by considering the duration of the effect after single doses of steroids. Ribosomes returned to normal function between 6 and 12h after the administration of corticosterone (20mg/kg), but still had decreased activity 12h after a similar dose of prednisolone. Normal ribosomal function was renewed between 12 and 18h after the administration of triamcinolone and betamethasone at 5mg/kg, but decreased activity persisted for more than 48h after similar doses of dexamethasone or triamcinolone acetonide. 4. There was no difference in the rate of incorporation of amino acids into nascent protein on polyribosomes from muscle of control animals and animals treated 6h previously with triamcinolone acetonide or dexamethasone. 5. The rate of weight gain of the heart was not affected by any of the steroids tested and heart ribosomes maintained normal activity although concentrations of steroids in this organ 5min after administration were 2-3 times that in skeletal muscle. 6. Mitochondria, isolated from the muscle of animals that had received triamcinolone acetonide (20mg/kg) 12h previously, were shown, by using a Coulter counter, to be enlarged. Nevertheless oxidation was only slightly uncoupled 12h after drug administration and they had normal function 6h later. Similar results with respect to mitochondrial function were obtained after the administration of dexamethasone (20mg/kg) and betamethasone (20mg/kg). 7. From these results it is concluded that the mitochondria are not functionally involved in the early phase of steroid-induced muscle catabolism. The observed decrease in the incorporating ability of muscle ribosomes in vitro appears to be much more closely linked to the initial catabolic event.