CHLORO-S-TRIAZINE ANTAGONISM OF ESTROGEN ACTION - LIMITED INTERACTIONWITH ESTROGEN-RECEPTOR BINDING

In an accompanying article (see pp. 183-196), it was reported that adm inistration of very high doses of the chlorotriazine herbicides atrazi ne, simazine, and diaminochlorotriazine (DACT), a common metabolite, e xpressed antiestrogenic activity in uteri of female Sprague-Dawley rat s without expressing intrinsic estrogenic activity. In the present art icle, studies of chlorotriazine interaction with rat uterine estrogen receptors (ER) are reported. Under equilibrium conditions, none of the triazine compounds showed an ability to compete against binding of ra diolabeled estradiol to ER. A weak competition was evident only if cyt osols were preincubated with triazines at 25 degrees C prior to introd uction of tracer. Competition was very weak, with k(l) estimates of 10 -100 mu M. A limited Scatchard analysis suggested a competitive type o f inhibition. Sucrose gradient analysis of cytosol incubations showed that triazine interaction with the 4S isoform of ER may be greater tha n with the 8S form. When administered to ovariectomized rats for 2 d a t 300 mg/kg/d, atrazine, simazine, or DACT all reduced uterine ER bind ing capacity by approximately 30%. Results from the receptor binding s tudies indicated that triazine competition against ER binding occurred to a much lesser degree than inhibition of estrogen-mediated response s reported in accompanying articles. This suggests that the complete r esponses to triazines may include inhibition of events other than or i n addition to ER binding of estrogen.