Dietary Energy, Glucocorticoids and the Regulation of Long Bone and Muscle Growth in the Rat

Abstract

1. The influence of dietary energy restriction and corticosterone on long bone and muscle growth, and their interrelationships, was studied in rats fed a range of restricted amounts of diets containing increasing concentrations of protein, thus maintaining constant protein intakes. Tibial length and epiphyseal cartilage width were measured radiographically. 2. In experiment 1, tibial length and gastrocnemius muscle growth were examined in ad libitum fed rats and during 4 days of severe energy restriction (25% ad libitum intake), starvation and ad libitum feeding with corticosterone treatment (10 mg/100 g), a mediator of the response to energy restriction. Weight loss occurred in all groups. Tibial growth continued in the 25% and starvation groups albeit at reduced rates with the inhibition of starvation > 25% group (P < 0.05), but was arrested after 2 days of corticosterone treatment. 3. Muscle growth inhibition was proportional to tibial growth inhibition of the 25% group, insofar as the muscle/bone ratio (W/L3.85), was maintained. This inter-relationship between muscle and bone growth previously reported for ad libitum high-protein-fed rats, is likely to reflect the anabolic influence of bone on muscle via passive muscle stretching induced by length growth. For both starvation and corticosterone groups the muscle/bone ratio fell (P < 0.05 compared with the ad libitum group), suggesting that muscle growth inhibition included an additional direct catabolic influence of starvation and corticosterone treatment. 4. In experiment 2, measurements of bone, muscle and liver growth were made in rats fed 75%, 50% and 25% ad libitum intakes and fed ad libitum intakes with corticosterone treatment for 8 days. Although body weight growth was arrested in all groups with weight loss in the 50%, 25% and corticosterone groups (P < 0.05), some tibial length growth continued at all levels of energy restriction, with significant reductions in length in the 50% and 25% groups at 4 days and in all groups at 8 days. Corticosterone treatment immediately arrested length growth. The epiphyseal cartilage widths of all restricted groups were significantly reduced at 4 days, graded with the degree of restriction, with corticosterone treatment most marked. 5. Muscle growth continued at near normal rates in the 75% and 50% groups, slowing only after 4 days, but was arrested in the corticosterone and 25% group with weight loss by 4 days in the corticosterone group and after 4 days in the 25% group. Muscle growth appeared relatively resistant to direct inhibition by energy restriction, following tibial growth in all restricted groups in that the muscle/bone ratios were initially maintained in all energy-restricted groups, falling only with the corticosterone treatment or 8 days of 50% and 25% intakes. In contrast, liver lost weight in all restricted groups during the first 4 days. 6. The results show a graded delayed inhibitory influence of energy deficiency on bone growth, which may be mediated by corticosteroids given the marked inhibitory influence of corticosterone. The relative resistance of muscle growth to energy restriction during liver and body-weight loss, is consistent with a powerful physiological anabolic stimulus of muscle stretching by bone length growth that appears to override any dietary-induced catabolic influence.