Diethylstilbestrol and other estrogens in the environment

Many environmental agents of diverse chemical structure possess estrogenic activity. Other hormonal activities do not seem to be so widespread through different chemical classes. Some compounds such as the mycotoxin, zearalenone, are metabolized from weakly active to more estrogenic forms and may thus be considered proestrogens. Metabolism of potent xenobiotics, such as diethylstilbestrol (DES), may result in relatively less hormonally active compounds as well as reactive intermediates associated with long-term toxicities. Weakly estrogenic xenobiotics may be physiologically significant if they persist in the body or when there is continuous exposure; some compounds with no apparent estrogen-receptor-binding affinity may exert estrogenic effects through indirect mechanisms. Estrogenic materials as part of the environment derive from natural (e.g., plant estrogens or mycotoxins) and synthetic (e.g., DES or DDT) sources. In some cases, environmental compounds may be potent estrogens which are used for their hormonal activity, or in other cases, they are weak estrogens in which hormonal activity is an inadvertant function; an example of the former case is DES as a growth-promoting agent for cattle, an example of the latter, kepone. Elucidation of the structural basis of estrogenic activity is the critical step awaited in this area.