The inhibition of human adrenal steroidogenic enzyme activities by suramin.

Published

Journal Article

Suramin has recently been used to treat patients with acquired immune deficiency syndrome because of the action of this 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 activities were measured in the presence of 0-5000 mumol/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 mumol/L; 17 alpha-hydroxylase activity, 25 mumol/L; 17,20-desmolase activity, 50 mumol/L; 11 beta-hydroxylase, 2 mumol/L, and 3 beta-hydroxysteroid dehydrogenase/isomerase, 1200 mumol/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.

Full Text

Duke Authors

Cited Authors

  • Ashby, H; DiMattina, M; Linehan, WM; Robertson, CN; Queenan, JT; Albertson, BD

Published Date

  • February 1989

Published In

Volume / Issue

  • 68 / 2

Start / End Page

  • 505 - 508

PubMed ID

  • 2465303

Pubmed Central ID

  • 2465303

International Standard Serial Number (ISSN)

  • 0021-972X

Digital Object Identifier (DOI)

  • 10.1210/jcem-68-2-505

Language

  • eng

Conference Location

  • United States