Abstract
Abstract Flutamide, a nonsteroidal antiandrogen, was found to be an effective inducer of δ-aminolevulinate synthetase, the rate-limiting enzyme in the heme biosynthetic pathway, in cultured chick embryo liver cells. This antiandrogen increased the activity of the enzyme 24-fold at a concentration of 1 μM and maximally stimulated the enzyme (62-fold) at a concentration of 50 μM. The steroidal antiandrogen, 6α-bromo-17α-methyl-17β-hydroxy-4-oxa-5α-androstan-3-one, did not stimulate aminolevulinate synthetase activity in these cells. Studies with inhibitors suggest that the induction of aminolevulinate synthetase by flutamide requires continued RNA and protein synthesis. In addition, the induction of the enzyme was inhibited (85%) by 15 μM hemin, the physiological repressor of aminolevulinate synthetase.
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