The effects of catabolic and anabolic steroids on amino acid incorporation by skeletal-muscle ribosomes

Abstract

1. A method is described for the routine isolation of ribosomes from small quantities of skeletal muscle that have been homogenized with the Ultra-Turrax tissue disintegrator. 2. Ribosomes prepared by this method from rats receiving triamcinolone acetonide or rabbits receiving cortisone acetate show a marked fall in their ability to incorporate amino acids when compared with ribosomes from control animals. 3. This fall in activity can be partially prevented in rats by pretreating the animals with an anabolic steroid, steroid 36644-Ba. 4. Testosterone (5mg./kg.) administered to rabbits in conjunction with cortisone acetate is not effective in maintaining ribosomal activity. However, steroid 36644-Ba at onetenth of an equiandrogenic dose (0-05mg./kg.) is extremely effective. 5. The results with ribosomes isolated from rabbits support the concept that steroid 36644-Ba and possibly all anabolic steroids have an ability to counteract the catabolic action of corticosteroids that is greater than their androgenic activity would suggest.It has been known for some years that androgens (anabolic steroids) are clinically useful for counteracting and controlling the undesirable effects of chronic corticosteroid therapy. The subject has been reviewed by Reifenstein (1956 WVhite (1967) that the amino acid-incorporating ability of ribosomes (called in the present paper P ribosomes) isolated from the psoas muscle of rats fell after Al-9oc-fluorohydrocortisone 16ac,17c-acetonide (triamcinolone acetonide) had been given in vivo, and that pretreatment of the animals with the anabolic compound 17fl-hydroxy-170c-methylandrosta-1,4-dien-3-one (methandionone or methandrostenolone) enabled full ribosomal activity to be retained. In the present paper these results have been extended by the examination of another anabolic steroid (steroid 36644-Ba) composed of 14 17, -hydroxy -7oc,17c -dimethyl -A -nor -B homooestrane-3,6-dione (I) in equilibrium with its enol form (II).One of the most important questions in the clinical use of anabolic steroids is whether their ability to antagonize the catabolic effects of glucocorticoids is due solely to their androgenicity. On the basis of the levator ani assay (Hershberger, Shipley & Meyer, 1953), which uses the castrated male rat, steroid 36644-Ba, administered subcutaneously, was 150-500 times more efficient than methyltestosterone in restoring the weight of the levator ani muscle to normal, but only 2-5-10 times more potent than methyltestosterone in restoring the weight of the seminal vesicles and ventral prostate (Desaulles & Schar, 1967). Thus the compound can be said to have an anabolic to androgenic ratio between 15 and 200.To see whether steroid 36644-Ba has an anticatabolic to androgenic ratio in a similar range, experiments were carried out with ribosomes from rabbits that had been pretreated with cortisone acetate. A regimen for drug administration was used (Little, 1966) in which cortisone acetate was administered to rabbits for 2 weeks followed by a 2-week period in which the animals...

Effects of Corticosteroid on Muscle Fibers and Intramuscular Connective Tissues in Mice.

“…It was reported that atrophy induced by corticosteroid is due to accelerated break down and decreased synthesis of muscle protein [10][11][12] . Shoji, et al reported that corticosteroid inhibits intramuscular ATP synthesis in the pathogenesis of steroid myopathy 13) .…”

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

“…Ribosomes isolated from the predominantly white hind-limb muscles ofadult male rats have a decreased ability to incorporate amino acids into protein in vitro when the animals have previously been treated with the powerful catabolic agent triamcinolone acetonide (9a-fluoro-1l1l,21-dihydroxy-16ac,17ao-isopropylidenedioxypregna -1,4 -diene -3,20 -dione) (White, 1967;Bullock et al, 1968;Peters et al, 1970;Bullock et al, 1971). Similar results were obtained when rabbits were given cortisone (Bullock et aL, 1968). The ribosomal defect develops comparatively rapidly (4-6h) after the administration of Vol.…”

“…The ribosomal defect develops comparatively rapidly (4-6h) after the administration of Vol. 127 the catabolic agent to rats (Peters et al, 1970) and can be fully or partially reversed by treating the animals with steroids that have an anabolic action (White, 1967;Bullock et al, 1968Bullock et al, , 1971. From this it would appear likely that the dysfunctional state of the ribosomes reflects events in the cell that are primary determinants of steroid-induced muscle catabolism.…”

Activity of skeletal-muscle ribosomes from intact and castrated rats treated with triamcinolone acetonide

“…In each experiment ribosomes were isolated from five control animals (intact or castrated) and five drug-treated animals 12h after the administration of the drug. The amino acidincorporating ability in vitro of the ribosome preparation from each animal was measured over a 20min incubation period in the presence of diluted liver cell sap and energy (Bullock, White & Worthington, 1968). The method for the isolation of ribosomes was essentially as described previously (Peters, Richardson, Small &;White, 1970) except that 0.1 M-tris buffer was used in the homogenizing medium and treatment with amylase was omitted.…”