Further evidence for the participation of 5 beta-steroids in the development of a porphyria induced by hexachlorobenzene.

Adult female rats were fed with a diet containing hexachlorobenzene to induce a porphyria. 5 alpha/5 beta-ratios of androstane steroids in blood were 0.61 +/- 0.13 in porphyric rats and 1.05 +/- 0.35 in normal rats. Etiocholanolone treatment of rats was ineffective in generation of a porphyria. The activity of microsomal glucuronyltransferase increased from 0.20 +/- 0.04 mU/mg to 0.77 +/- 0.23 mU/mg by this treatment. Administration of Flutamide (4'-nitro-3'-trifluoromethylisobutyranilide) to porphyric rats resulted in a decline of porphyrin excretion by 55%. The hepatic NADH-5 beta-reductase was strongly inhibited by this drug, whereas NADPH-5 beta-reductase displayed a slightly increased activity. These findings are further evidence for the involvement of 5 beta-steroids in the formation of porphyria.