Chloro‐s‐triazine antagonism of estrogen action: Limited interaction with estrogen receptor binding
作者:
MarieK. Tennant,
D. Scott Hill,
J. Charles Eldridge,
LawrenceT. Wetzel,
CharlesB. Breckenridge,
JamesT. Stevens,
期刊:
Journal of Toxicology and Environmental Health
(Taylor Available online 1994)
卷期:
Volume 43,
issue 2
页码: 197-211
ISSN:0098-4108
年代: 1994
DOI:10.1080/15287399409531915
出版商: Taylor & Francis Group
数据来源: Taylor
摘要:
In an accompanying article (see pp. 183–196), it was reported that administration of very high doses of the chlorotriazine herbicides atrazine, simazine, and diaminochlorotriazine (DACT), a common metabolite, expressed antiestrogenic activity in uteri of female Sprague‐Dawley rats without expressing intrinsic estrogenic activity. In the present article, 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 radiolabeled estradiol to ER. A weak competition was evident only if cytosols were preincubated with triazines at 25°C prior to introduction of tracer. Competition was very weak, with ktestimates of 10–100 μM. A limited Scatchard analysis suggested a competitive type of inhibition. Sucrose gradient analysis of cytosol incubations showed that triazine interaction with the 4S isoform of ER may be greater than with the 85 form. When administered to ovariectomized rats for 2 d at 300 mg/kg/d, atrazine, simazine, or DACT all reduced uterine ER binding capacity by approximately 30%. Results from the receptor binding studies indicated that triazine competition against ER binding occurred to a much lesser degree than inhibition of estrogen‐mediated responses reported in accompanying articles. This suggests that the complete responses to triazines may include inhibition of events other than or in addition to ER binding of estrogen.
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