TESTOSTERONE-INDUCED FOCAL MYOCARDITIS IN RATS I. : MORPHOLOGICAL AND BIOCHEMICAL STUDIES WITH SPECIAL REFERENCE TO PATHOGENETICAL MECHANISM AND SPECIES DIFFERENCES.

Abstract

Focal myocarditis characterized by interstitial edema, round cell infiltration and fibrosis occurred in rats given a subcutaneous administration of testosterone propionate in a dose of 50 mg/kg for 30 consecutive days or longer. Biochemical analysis showed a two to five time increase of deoxycorticosterone and a moderate decrease of corticosterone in blood plasma of these rats as well as in those treated with 50 mg/kg of testosterone propionate for 15 days. It was also shown that myocarditis did not occur in adrenalectomized rats after administration of testosterone propionate 50 mg/kg for 30 days, while subcutaneous injections of deoxycor-ticosterone acetate in a dose of 15 mg/kg for 30 days invariably produced cardiac lesions in both adrenalectomized rats and sham-operated rats. Regarding species difference, administration of testosterone did not produced either a high blood level of deoxycorticosterone or focal myocarditis in guinea pigs or rabbits. From these results, it is concluded that focal myocarditis in rats after administration of large amounts of testosterone propionate is related to the elevation of deoxycorticosterone in blood plasma but not to the direct effects of testosterone propionate on the myocardium.