INHIBITION OF RAT STEROID 5-ALPHA-REDUCTASE (ISOZYME-1) BY SURAMIN

In this study, we show the inhibition of rat steroid 5 alpha-reductase (isozyme 1) by suramin. The enzyme activity decreased in a dose-depen dent manner as suramin concentrations increased with the calculated dr ug dose required for 50% inhibition (at 5 mu M testosterone and 200 mu M NADPH) being 13 mu M. Suramin showed non-competitive inhibition of 5 alpha-reductase with respect to testosterone (K-1(T) = 2.4 mu M) and competitive inhibition with respect to NADPH (K-i(NADPH) = 220 nM). F urthermore, suramin and NADP(+), but not NAD(+) protected 5 alpha-redu ctase from labeling by 2-azido-NADP(+), a photoactive probe which has recently been used to identify the NADPH binding domain of 5 alpha-red uctase. These results suggest that suramin inhibits rat steroid 5 alph a-reductase (isozyme 1) at the level of NADPH binding to the enzyme.