Estrogenic Activity of the Mycotoxins Zearalenone and Zearalanol in the Neonatal Rat Uterus

摘要

The mycotoxins zearalenone and zearalanol elicit adverse estrogenic effects in several commercially important animal species. Since other estrogens can irreversibly alter target tissue development, the authors investigated the estrogenic activity of these compounds in the neonatal rat uterus. Both mycotoxins induced dose-dependent premature uterine growth when injected daily on postnatal days 1-5, with an ED50 of 1.3 mg/kg BW. Nuclear estrogen receptor levels dramatically increased 1 hour after either a single injection on day 5 or after five daily injections. In 5 day old animals, the nuclear translocated receptor was characterized as a single class of binding sites with a KD for estradiol (E2) of 1 nM. Maximal nuclear levels occurred at 30-60 minutes after injection of either compound. At 6 hours, zearalanol-treated animals retained about twice the level of nuclear estrogen receptor as zearalenone-treated animals. In 5-day old animals, a single mycotoxin dose (10 mg/kg BW) maximally induced ornthine decarboxylase (ODC) at 6 hours to 5-fold above control ODC levels. However, in dose-response studies zearalanol was 10-100 fold more effective in ODC induction than zearalenone. We conclude that the uterine growth response and ODC induction demonstrate the estrogenic action of these mycotoxins, which appear to be mediated via the estrogen receptor.