The sedimentation of rat skeletal-muscle ribosomes. Effect of hydrocortisone, insulin and diet

Abstract

1. The influence of hydrocortisone, insulin and diet on the size distribution of ribosomes in a post-mitochondrial supernatant prepared from rat skeletal muscle was studied by sedimentation analysis with a linear 15-40% (w/v) sucrose gradient. 2. Within 4hr. after the injection of 5mg. of hydrocortisone to well-nourished rats, a decrease in the yield per g. of muscle and proportion of total RNA due to polyribosomes was observed. Similar results were obtained in rats given a protein-free diet for 3 days before administration of the hormone. 3. Insulin injection increased the yield and proportion of polyribosomes within 2hr. and decreased the proportion of the lighter ribosomal aggregates. Similar results were noted in rats given a protein-free diet for 3 days before injection. A protein-free diet given for 3 days decreased the yield and proportion of polyribosomes. Insulin did not increase the yield of polyribosomes if rats were starved for 52hr. before injection, but decreased the yield and proportion of the lighter ribosome species. 4. A 52hr. period of starvation or 2,4-dinitrophenol (15mg./kg. body wt.) given 1hr. before the rats were killed resulted in a decreased yield and proportion of polyribosomes, and, within 6hr. of re-feeding the rats with protein-free diets, an increased concentration of polyribosomes was noted. 5. The effects of a protein-free diet, hydrocortisone and insulin on the sedimentation of muscle ribosomes were found to be in accord with their net effects on muscle protein synthesis.

Glucocorticoid action on protein synthesis and protein breakdown in isolated skeletal muscles

“…The rapid suppression of protein synthesis (i.e. 3 h; Table 1B) is in keeping with the suggestion that the acute response to these steroids is a decrease in the initiation of translation (Rannels & Jefferson, 1980) and is accompanied by a rapid (4h) decrease in the proportion of polyribosomes (Young et al, 1968;Bullock et al, 1972). Such initial responses are followed by an inhibition of transcription and consequent decreases in the muscle's RNA content.…”

“…These and previous studies in vitro suggest a common and concerted mode of action of the glucocorticoids in arresting muscle growth. DNA synthesis (Goldberg & Goldspink, 1975), the net transfer of amino acids (Kostyo & Remond, 1966;Lewis & Goldspink, 1981) and the rates of protein synthesis (Tables 1 and 2; Young et al, 1968) and protein breakdown (Tables 1 and 2) are all significantly inhibited in skeletal muscle within 4 h of exposure to these steroid hormones.…”

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

“…3). Our results pow support those of Young et al (1968), who showed a decrease in the polyribosome content of ribosomes from young rats treated with cortisol.…”

On the Cellular Regulation of Growth and Development in Skeletal Muscle

“…Although there is no direct correlation between the protein-synthesizing activity of such preparations and declining rates of muscle growth with age (Section IV/I), changes in the rate of synthesizing muscle protein are usually accompanied by changes in the activity and state of aggregation of isolated ribosomes when the nutritional and hormonal status of animals is altered experimentally (cf . Breuer & Florini, 1965;Florini & Breuer, 1966;Wool et al, 1968;Young & Alexis, 1968;Young, Chen & Macdonald, 1968 ; Bullock et al, 1972).…”