Possible androgenic/anti-androgenic activity of the insecticide fenitrothion

To date, within the field of endocrine disruption, much focus has been plac ed on chemicals that mimic oestrogens (so-called xenoestrogens), and the nu mber of such chemicals apparently detected continues to grow steadily, Less effort has been expended on investigating chemicals that mimic, or antagon ize, other hormones, Nevertheless, a number of chemicals have been reported to have a weak affinity for the androgen receptor, all of which have, to d ate, been found to have anti-androgenic activity in vivo, In this report, w e present evidence that the insecticide fenitrothion can interact with the androgen, but not with the oestrogen, receptor, Using recombinant yeast exp ressing the human androgen receptor, we found that fenitrothion behaved as an androgen agonist in vitro when tested alone, and that it could antagoniz e the androgen DHT when both chemicals competed for the androgen receptor i n vitro. In vivo studies using both intact and castrated male rats showed n o conclusive androgenic or antiandrogenic responses, Changes in organ weigh ts suggestive of anti-androgenic effects were mitigated against by the redu ced body weights of fenitrothion-treated rats. The toxicity of the compound precluded the use of higher dose levels to substantiate any tentative find ings. Interestingly, fenitrothion (and related insecticides) is structurall y similar to flutamide, an anti-androgen used clinically that gives clearly positive responses in both intact and castrated rats, Copyright (C) 2001 J ohn Wiley & Sons, Ltd.