Possible androgenic/anti-androgenic activity of the insecticide fenitrothion.
To date, within the field of endocrine disruption, much focus has been placed on chemicals that mimic oestrogens (so-called xenoestrogens), and the number of such chemicals apparently detected continues to grow steadily. Less effort has been expended on investigating chemicals that mimic, or antagonize, other hormones. Nevertheless, a number of chemicals have been reported to have a weak affinity for the androgen receptor, all of which have, to date, been found to have anti-androgenic activity in vivo. In this report, we present evidence that the insecticide fenitrothion can interact with the androgen, but not with the oestrogen, receptor. Using recombinant yeast expressing the human androgen receptor, we found that fenitrothion behaved as an androgen agonist in vitro when tested alone, and that it could antagonize the androgen DHT when both chemicals competed for the androgen receptor in vitro. In vivo studies using both intact and castrated male rats showed no conclusive androgenic or anti-androgenic responses. Changes in organ weights suggestive of anti-androgenic effects were mitigated against by the reduced body weights of fenitrothion-treated rats. The toxicity of the compound precluded the use of higher dose levels to substantiate any tentative findings. Interestingly, fenitrothion (and related insecticides) is structurally similar to flutamide, an anti-androgen used clinically that gives clearly positive responses in both intact and castrated rats.
Sohoni
P
P
Department of Biological Sciences, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK.
Lefevre
P A
PA
Ashby
J
J
Sumpter
J P
JP
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D005278:Fenitrothion / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D015003:Yeasts
D000728:Androgens; D007306:Insecticides; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D005278:Fenitrothion