Fenarimol

Aromatase inhibitors prevent the conversion of androgens to estrogens. This P450 enzyme is highly conserved in a wide variety of tissues and many species, but the overall homology of the gene with other cytochrome P450s is only about 30%. Hence, this enzyme is considered to be in a separate gene family within the overall superfamily. As a consequence of the lack of sequence homology with other P450 enzymes in the steroid pathway, inhibitors of aromatase can display more specific activities than drugs like ketoconazole. In this regard, aro-matase inhibitors have significant clinical uses and often present fewer untoward effects on other endocrine organs. Several fungicides like fenarimol inhibit aromatase activity [196] in mammals, resulting in infertility in both sexes. In our study, fenarimol was administered daily by gavage from weaning, through puberty, mating, gestation and lactation to the P0 generation (at 0,17.5, 35, or 70 mg/kg/day) while the F1 offspring were only exposed indirectly through the placenta and milk. Fenarimol treatment inhibits male rat mating behavior (some males would not mount a sexually receptive female rat) in the P0 generation, presumably by inhibiting the conversion of androgens to estrogens in the brain [20]; it also inhibits parturition in P0 female rats because of the critical role of estrogens near term in the induction of labor in this species. Although fertility in the P0 generation was reduced by fenarimol treatment, the F1 generation, exposed indirectly only during pregnancy and during lactation, was unaffected. This pesticide also has effects in invertebrates, inhibiting ecdys-teroid synthesis [197], while in reptiles, other aromatase inhibitors inhibit female gonadal sex determination [120].

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