The Inhibition of Human Adrenal Steroidogenic Enzyme Activities by Suramin*

Abstract

Suramin has recently been used to treat patients with acquired immune deficiency syndrome because of the action of the drug on reverse transcriptase. Patients so treated developed the symptoms and hormonal profiles of adrenal insufficiency. To evaluate the mechanism of action of suramin on adrenalcortical function, adrenal mitochondrial and microsomal preparations from five subjects were assayed for steroidogenic enzyme activity in the presence and absence of suramin. Specifically, 3.beta.-hydroxysteroid dehydrogenase/isomerase, 17.alpha.-hydroxylase, 21-hydroxylase, 11.beta.-hydroxylase, and 17,20-desmolase activity were measured in the presence of 0-5000 .mu.mol/L suramin concentrations. In all assays, enzyme activities decreased in a dose-dependent fashion as suramin concentrations increased. The drug doses (calculated) that caused 50% inhibition of enzyme activity were: 21-hydroxylase activity, 50 .mu.mol/L; 17.alpha.-hydroxylase activity, 25 .mu.mol/L; 17,20-desomolase activity, 50 .mu.mol/L; 11.beta.-hydroxylase, 2 .mu.mol/L, and 3.beta.-hydroxysteroid dehydrogenase/isomerase, 1200 .mu.mol/L. These results suggest that suramin has a concentration-dependent inhibitory effect on the key P-450-regulated enzymatic steps in adrenal glucocorticoid steroidogenesis, which may explain the development of adrenal insufficiency in acquired immune deficiency syndrome patients treated with suramin.