Pesticides interfere with the nongenomic action of a progestogen on meiotic maturation by binding to its plasma membrane receptor on fish oocytes.
Although many environmental contaminants disrupt endocrine function by binding to nuclear steroid receptors, it is not known whether they are capable of binding to steroid membrane receptors and interfering with nongenomic actions of steroids. The binding of several organochlorine pesticides to the plasma membrane receptor for the maturation-inducing steroid, 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), in the ovaries of spotted seatrout (Cynoscion nebulosus) was investigated in in vitro competition assays. Kepone and o,p'-DDD were competitive inhibitors of 20beta-S binding and caused concentration-dependent displacement of [3H]-20beta-S from its receptor site over the range of 10(-4) to 10(-6) or 10(-7) M, whereas several other pesticides had lower affinities for the receptor. Interference with the nongenomic actions of 20beta-S on final meiotic maturation of spotted seatrout oocytes (final oocyte maturation, FOM) was examined in an in vitro bioassay. A concentration-dependent inhibition of FOM in response to 20beta-S was observed after 5 min and 12 h exposure to the same range of Kepone and o,p'-DDD concentrations (10(-4) to 10(-6) or 10(-7) M). The close correspondence between competitive binding of the two pesticides to the 20beta-S membrane receptor and their inhibition of 20beta-S induced FOM suggests a mechanism of endocrine disruption mediated by binding to a steroid membrane receptor and antagonism of a nongenomic steroid action.
Das
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S
Department of Internal Medicine, Yale University, School of Medicine, VA Medical Center, West Haven, CT 06516, USA.
Thomas
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P
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism*; D007631:Chlordecone / Q000378:metabolism; D003350:Cortodoxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003634:DDT / Q000378:metabolism; D005260:Female; D007306:Insecticides / Q000009:adverse effects* / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects; D008731:Methoxychlor / Q000378:metabolism; D008939:Mitotane / Q000378:metabolism; D009865:Oocytes / Q000648:ultrastructure*; D010473:Perciformes; D011980:Receptors, Progesterone / Q000378:metabolism*
D007306:Insecticides; D011980:Receptors, Progesterone; C051954:17,20,21-trihydroxy-4-pregnen-3-one; D008939:Mitotane; D003634:DDT; D007631:Chlordecone; D008731:Methoxychlor; D003350:Cortodoxone