title: Influence of dietary protein, energy and corticosteroids on protein turnover, proteoglycan sulphation and growth of long bone and skeletal muscle in the rat.
abstract: 1. We report here the extent to which changes in protein turnover contribute to the previously described inhibition of growth of rat tibial length and skeletal muscle mass in response to protein deficiency [1], energy restriction and corticosterone treatment [2]. Measurements of 35S uptake in vivo also enabled the qualitative pattern of changes in proteoglycan synthesis in bone and muscle to be established. 2. Protein deficiency was examined by ad libitum feeding of 20%, 7%, 3.5% and 0.5% protein diets with measurements at 1, 3 and 7 days (all diets), and 14 and 21 days (0.5% protein). In bone this induced delayed inhibition of tibial growth with parallel inhibition of protein synthesis, as measured by the phenylalanine flooding dose method. This was mediated by reductions in both ribosomal capacity (RNA/protein ratio) and activity (protein synthesis/RNA) in the 0.5% protein group. The pattern of inhibition of proteoglycan sulphation, measured as 35S uptake 60 min after injection of a tracer dose of labelled sulphate, was similar to that of protein synthesis. 3. In muscle there was an intermediate graded inhibition of protein synthesis by protein deficiency, mediated by reductions in both ribosomal capacity and activity in the 0.5% protein group, which preceded growth inhibition in the 7% and 3.5% groups, and which was progressive with time. Transient increases in proteolysis contributed to the growth inhibition is some groups, but the rate fell eventually in the 0.5% group. The pattern of response of proteoglycan sulphation differed from protein synthesis with a delayed inhibition, but with subsequent marked reduction. 4. Energy restriction was induced by diets fed for 4 or 8 days at 75%, 50% and 25% ad libitum intakes with protein intakes held constant, and corticosterone treatment involved a dose of 10 mg day-1 100-1 g (subcutaneous) with ad libitum feeding. In bone this induced a pattern of length growth inhibition which was dissociated from inhibition of protein synthesis in the moderately restricted (75% and 50%) groups. Only in the 25% group and in the 8 day corticosterone group was protein synthesis inhibited, through reductions in ribosomal capacity and activity. 35S uptake was also dissociated from growth inhibition, with reduced 35S uptake observed only after corticosterone treatment or 8 days of the 50% or 25% diets. 5. In muscle the energy restriction and corticosterone treatment induced parallel inhibitions of growth and protein synthesis, mediated by similar graded reductions in the RNA/protein ratios and in the 25% group in the KRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Nutrition Research Unit, London School of Hygiene and Tropical Medicine, St Pancras Hospital, U.K.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Yahya
authors.forename: J O
authors.initials: JO
authors.lastname: Tirapegui
authors.forename: P C
authors.initials: PC
authors.lastname: Bates
authors.forename: D J
authors.initials: DJ
authors.lastname: Millward
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology*; D003677:Deficiency Diseases / Q000503:physiopathology*; D002149:Energy Intake / Q000502:physiology; D008297:Male; D024510:Muscle Development; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000254:growth & development*; D014176:Protein Biosynthesis; D011488:Protein Deficiency / Q000503:physiopathology; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013462:Sulfur Radioisotopes; D013977:Tibia / Q000254:growth & development
chemical_list: D009124:Muscle Proteins; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D003345:Corticosterone