High carbonyl reductase activity in adrenal gland and ovary emphasizes its role in carbonyl compound detoxication

Abstract

Carbonyl reduction has been studied in liver, kidney, adrenal gland and ovary of female Wistar and Sprague-Dawley rats as well as of female NMRI mice by using metyrapone as a substrate and by means of direct HPLC analysis of the reduced alcohol metabolite metyrapol. Carbonyl reducing activities were found in all tissues examined so far, with that in rat ovary and adrenal gland cytosol exceeding the liver cytosolic specific activity severalfold: 15-fold and 12-fold in the Wistar strain; 12-fold and 7-fold in the Sprague-Dawley strain, respectively. In general, Wistar rat enzyme activities were about four times higher than those of Sprague-Dawley rats in all fractions, which indicates an interesting genetic difference between the two rat strains. Due to the sensitivity towards the diagnostic inhibitor quercitrin, carbonyl reductase (EC 1.1.1.184) seems to be mainly responsible for metyrapone reduction in rat and mouse adrenal gland and ovary cytosol. However, sensitivity towards dicoumarol in microsomal fractions of mouse tissues points to the involvement of further carbonyl reducing enzymes. Western blot experiments revealed immunological differences between metyrapone reductase from liver microsomes and respective enzymes of all other tissues. In conclusion, the difference in tissue and intracellular distribution suggests that several enzymes are involved in carbonyl reduction of metyrapone and the intracellular multiplicity of the enzymes may have some relation to their significance in carbonyl compound detoxification. These results support the hypothesis that carbonyl reductases, besides their participation in the metabolism of physiologically occurring substances, provide the enzymatic basis for the detoxification of xenobiotic carbonyl compounds in adrenal gland and ovary which have escaped their metabolic conversion by the liver.