Prevention of Experimental Nephrosclerosis with Methyl-Testosterone

Abstract
Several observations suggest that testicular hormones exert a protective action upon renal tissue. The authors investigated, therefore, whether testosterone and other testoid compounds could inhibit the nephrosclerosis experimentally produced by desoxycorticosterone acetate (D.C.A.) adm. They performed an expt. on 48 [female] albino rats weighing 57-76 g. at the onset of the expt. These animals were subdivided into 6 groups each consisting of 8 rats. Groups I to III were left intact, while in Groups IV to VI the left kidney was removed at the beginning of the expt. All groups received 1% NaCl instead of drinking water. Groups I and IV, which served as intact and partially nephrectomized controls, respectively, received twice daily subcut. injs. of 5 mg. of finely ground cholesterol crystals suspended in 0.1 ml. of water. Cholesterol was given to the controls because this compound is not known to have any hormonal action yet is chemically related to the steroid hormones. Groups II, III, V and VI received twice daily subcut. injs. of 2 mg. of D.C.A. in 0.1 ml. of water. In addition to this, Groups III and VI also received twice daily subcut. injs. of 5 mg. of methyl-testosterone suspended in 0.1 ml. of water. All animals were killed on the 37th day of treatment at which time their kidneys were weighed and histologically examined. Expts. in the rat indicate that D.C.A. overdosage causes nephrosclerosis, especially in animals kept on a high NaCl intake. Both the morphological manifestations of nephrosclerosis, and the resultant proteinuria are inhibited by simultaneous treatment with methyl-testosterone. Unilaterally nephrectomized rats are particularly sensitive to the nephrosclerotic action of D.C.A. but even in these animals methyl-testosterone exerts a beneficial effect. The possible clinical implications of these observations are discussed.