Time course of the effect of catabolic doses of corticosterone on protein turnover in rat skeletal muscle and liver

Abstract

The time course of the response of protein synthesis in muscle and liver to catabolic doses of corticosterone (10 mg/day per 100 g body wt.) was studied in vivo in growing rats over a 12-day period. The rate of protein synthesis in muscle and liver and the rate of actomyosin synthesis in muscle were measured by the phenylalanine-flooding technique, and 3-methylhistidine (N tau-methylhistidine) synthesis was measured by injection of labelled histidine. 3-Methylhistidine concentrations in tissue free pools and urinary excretion were also measured to compare directly with the rate of muscle protein degradation determined as the difference between synthesis and growth each day during the treatment. The overall rate of protein synthesis in muscle fell gradually over the first 4 days, reaching a rate after 5 days that was 36% of the initial rate, and this lower rate was then maintained for the following week. This decrease in the overall rate was accompanied with changes in the relative rate of synthesis in muscle proteins, since during the first 4 days there was a disproportionate decrease in the rate of actomyosin synthesis, and specifically 3-methylhistidine synthesis. In the latter case the synthesis rate was decreased to only 4% of its initial rate after 4 days. These changes in protein synthesis in muscle were accompanied by a transient increase in the rate of protein degradation, which was more than doubled on days 2 and 3 of treatment but which returned to the original rate on day 5, and a similar pattern of response was indicated by urinary 3-methylhistidine excretion, which also exhibited a transient increase. Thus in this case 3-methylhistidine excretion and measured rates of protein degradation in muscle do correlate. The transient effects of the glucocorticoids on degradation compared with the sustained effect on synthesis suggest that these two responses are achieved by different mechanisms. The hepatic size and protein mass were increased by the treatment, and protein synthesis was well maintained until after 12 days, when the rate was suppressed. Although the fractional synthesis rate was transiently increased for 24 h, it is argued that the enlarged liver most likely reflects a decrease in protein degradation resulting from the increased amino acid supply to the liver. This would result from the cessation of muscle growth while dietary supply was maintained.

Glucocorticoid-induced insulin resistance of protein synthesis is independent of the rapamycin-sensitive pathways in rat skeletal muscle

“…As physiological insulin levels already maximally stimulate muscle protein synthesis in vivo, the difference in insulin-stimulated protein synthesis that we observed in vitro should also be found in vivo. The results of both Odedra et al (1983) and Southorn et al (1990) agree with this. They demonstrated that the responsiveness of muscle protein synthesis to insulin was altered when rats were treated with steroids and that insulin infusion in vivo did not counteract the decrease in muscle protein synthesis.…”

“…Glucocorticoids have direct effects on muscle protein turnover by either inhibiting protein synthesis (Tomas et al 1979, Rannels & Jefferson 1980, McGrath & Goldspink 1982, Odedra et al 1983, Kayali et al 1987 or increasing proteolysis (Tomas et al 1979, McGrath & Goldspink 1982, Kayali et al 1987. However, in vivo, they also act through their interaction with insulin.…”

“…The association of glucocorticoid excess and muscle atrophy is now well established, and the mechanisms underlying muscle wasting consistently involve inhibition of skeletal muscle protein synthesis and/or increased proteolysis (Tomas et al 1979, Rannels & Jefferson 1980, McGrath & Goldspink 1982, Odedra et al 1983, Kayali et al 1987. However, glucocorticoid-induced muscle atrophy may result from both the steroid effect per se and/or modification of anabolic hormone action on protein metabolism (i.e.…”

Heat stress amelioration and production performance in layers supplemented with herbal liquid anti-stressor product

“…Before treatment in all birds, higher levels of serum cortisol (mg/L) content was found indicating the effect of high temperature and relative humidity. High ambient temperature induces production and release of corticosteroids (Siegal, 1980), exerts catabolic effects (mobilization of proteins and lipids) through muscle wasting and reduces growth rate (Sujatha et al, 2010;Odedra et al, 1983;Hayashi et al, 1994). Similar results were obtained in the present study, where serum cortisol levels (Table 3) were significantly (P≤0.05) higher in the control as compared to the treatment groups.…”

The Activated Glucocorticoid Receptor Modulates Presumptive Autoregulation of Ribosomal Protein S6 Protein Kinase, p70 S6K

“…As is starkly manifest in Cushing's syndrome, an endocrinopathic anomaly characterized by glucocorticoid overproduction, glucocorticoid excess is associated with atrophy of the skeletal musculature and derives from both the acceleration of protein degradation (70 -72) and attenuation of mRNA translation rates (73)(74)(75)(76). In vivo, 4 h of exposure to glucocorticoids is sufficient to reduce p70 S6K activation, hinder assembly of the eukaryotic translation initiation factor 4F complex, and suppress global protein synthesis in skeletal muscle (40), suggesting that glucocorticoids acutely and negatively affect protein biosynthesis at the level of translation initiation.…”