Abstract
Although zearalenone (ZEN) produced by Fusarium species lacks estrogen-like structure, this mycotoxin exhibits estrogen-like effects on domesticated animals, particularly swine, and may contribute to the overall load of environmental estrogens. To clarify the mode of action of ZEN, we investigated the interaction of ZEN with the estrogen receptor (ER) and its effect on nuclear RNA polymerase activities and protein synthesis in the rat uterus. The results showed that ZEN and its analogs could albeit poorly bind to the rat uterine and brain ERs in vivo and in vitro, and their binding ability was of following order: α-zearalanol (α- ZAL)>α-zearalenol (α-ZEL)>β-ZAL>ZEN>β-ZEL. RNA polymerase activities in the uterine nuclei isolated from ZEN-treated rats were enhanced 4-fold of the vehicle control. Furthermore, a 52-kDa protein was specifically induced immediately after the addition of ZEN and its derivatives such as α-ZEL and α-ZAL to the immature rat uteri in vivo and in vitro. On the other hand, the induction of 52-kDa protein was hardly detected in the presence of RNA polymerase inhibitors including α-amanitin and actinomycin D, suggesting that ZEN and its analogs-ER complexes might act as a transcriptional activating factor. These findings clearly indicate that ZEN and its analogs, despite their non-steroidal structure, exhibit an estrogenic activity toward target tissues in a similar manner to that of natural estrogens. In addition, the binding ability of ZEN to the rat brain ER could assume the possibility that ZEN affects the estrogen feedback system in the rat brain to result in the shrinkage of ovary and testis and participates in behavioral abnormalities.
