Disparate effects of diethylstillbestrol and prednisolone on enzyme efflux from heart and skeletal muscle
Morgan, J.; Cohen, L.; Bozyk, M.E.; Bittner, S.
Research Communications in Chemical Pathology and Pharmacology 15(1): 149-170
1976
ISSN/ISBN: 0034-5164 PMID: 968173 Document Number: 100424
Diethylstilbestrol (DES) almost always and prednisolone (Pr), less frequently, lowered the high serum enzyme activities in Duchenne's muscular dystrophy (DMD). Pretreatment of mice with each of these agents lowered enzyme efflux from isolated skeletal muscle incubated in vitro, but efflux was augmented by higher doses of Pr. These agents may influence skeletal muscle enzyme efflux in man, producing the effects noted in DMD. The effect on enzyme efflux from skeletal muscle and heart that these 2 agents would exert when given in combination were assessed. Four groups of mice (14/group) were injected with saline, 250 .mu.g DES, 35 .mu.g Pr or 250 .mu.g DES and 35 .mu.g Pr in saline every other day for 22 days. The left gastrocnemius and heart were isolated from animals of each group and placed in separate tubes containing incubation medium at 25.degree. C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which issued from each organ was determined over a 5 h period. In the doses tested, DES selectively reduced enzyme efflux from skeletal muscle but had no effect on enzyme efflux from heart; a Pr dose which decreased enzyme efflux from the heart augmented efflux from the gastrocnemius and DES prevented the enhanced enzyme efflux produced by Pr. These hormones, in pharmacological doses, apparently influenced enzyme efflux from muscle. These hormones probably exert a similar physiological role. This experimental model appears to be useful in assessing the effects of single agents and agents in combination, on enzyme efflux and should be of aid in selecting appropriate agents which may be therapeutically useful in Duchenne's muscular dystrophy.