Hormonal regulation of microsomal flavin-containing monooxygenase: tissue-dependent expression and substrate specificity

Abstract

The substrate- and tissue-dependent hormonal regulation of flavin-containing monooxygenase (EC 1.14.13.8) was studied in male and female rats. Hypophysectomy of males reduced liver microsomal N,N-dimethylaniline N-oxidation, thiobenzamide S-oxidation, and imipramine N-oxidation, although the reduction was not as marked with the latter substrate. Castration also reduced flavin-containing monooxygenase-dependent activities, but not to the same extent as hypophysectomy. Administration of growth hormone or testosterone to hypophysectomized males only partially restored basal activities. In female rats, hypophysectomy had no effect on N,N-dimethylaniline N-oxidation or thiobenzamide S-oxidation and actually stimulated imipramine N-oxidation (98%). These effects were demonstrated to be tissue- and sex-dependent. For example, hypophysectomy markedly (300%) enhanced imipramine N-oxidation in male kidney and significantly decreased the same activity in male and female lung. Correlations between levels of the enzyme determined by immunoquantitation (with antibody to the rat liver enzyme) and activities toward these three substrates, in male and female liver, lung, and kidney, also provide evidence for the existence of multiple forms of flavin-containing monooxygenase, which appear to be under different hormonal regulation.