ESTROGENIC ACTION OF DDT AND ITS ANALOGS

被引:275
作者
WELCH, RM
LEVIN, W
CONNEY, AH
机构
[1] The Wellcome Research Laboratories, Burroughs Wellcome and Co. (U.S.A.) Inc., Tuckahoe
关键词
D O I
10.1016/0041-008X(69)90117-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The intraperitoneal injection of 50 mg/kg of purified o,p′-DDT, technical grade DDT, purified methoxychlor, or purified p,p′-DDT increased the uterine wet weight by 49, 43, 37, and 28%, respectively, 6 hours after injection. o,p′-DDD, m,p′-DDD, p,p′-DDD, and p,p′-DDE exhibited little or no activity. The intraperitoneal injection of as little as 5 mg/kg or 1 mg/kg of technical grade DDT or o,p′-DDT, respectively, caused a significant increase in the uterine wet weight in immature female rats. The injection of technical grade DDT or o,p′-DDT into ovariectomized adult rats also increased uterine wet weight, indicating that the effect of the DDT analogs was not mediated through the ovaries. Treatment of immature female rats with a 50 mg/kg injection of technical grade DDT or purified o,p′-DDT caused a severalfold stimulation in the incorporation in vitro of glucose-U-14C into lipid, protein, RNA, and acid-soluble constituents in the uterus 6 hours after the dose of DDT. A smaller stimulatory effect was observed with purified p,p′-DDT. Treatment of rats with technical grade DDT, purified o,p′-DDT, methoxychlor or p,p′-DDT 2 hours before an injection of estradiol-17β-6,7-3H inhibited the uptake of estradiol-17β-6,7-3H by the uterus in vivo, possibly by competing for sites that bind estradiol-17β in the uterus. o,p′-DDD, p,p′-DDD, m,p′-DDD and p,p′-DDE did not inhibit the uptake of estradiol-17β-6,7-3H by the uterus. Pretreatment of rats with carbon tetrachloride inhibited the uterotropic action of o,p′-DDT and technical grade DDT. This suggests the possibility that the action of these substances on the uterus may depend on the conversion of the analogs of DDT to estrogenic metabolites. © 1969.
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页码:358 / &
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