1-(o-chlorophenyl)-1-(p-chlorophenyl)2,2,2-trichloroethane: a probe for studying estrogen and progestin receptor mediation of female sexual behavior and neuroendocrine responses.
1-(o-chlorophenyl)-1-(p-chlorophenyl)2,2,2-trichloroethane: a probe for studying estrogen and progestin receptor mediation of female sexual behavior and neuroendocrine responses.
复制标题
1-(邻氯苯基)-1-(对氯苯基)2,2,2-三氯乙烷：用于研究雌激素和孕激素受体介导女性性行为和神经内分泌反应的探针。
DOI：
10.1210/endo-111-5-1498
复制
发表时间：
1982
期刊：
影响因子：
4.8
通讯作者：
A. M. Etgen
中科院分区：
文献类型：
--
作者：
A. M. Etgen
许多氯化杀虫剂已被证明与雌激素受体相互作用，并在外周生殖组织（如阴道和子宫）中模拟雌激素作用。本研究旨在评估二氯二苯基三氯乙烷（DDT）异构体o，p '-DDT在神经雌激素靶组织中是否具有雌激素或抗雌激素活性。单次皮下注射高达500 mg/kg o，p '-DDT对雌性性行为（脊柱前凸）没有影响。然而，更长时间的治疗诱导高水平的脊柱前凸行为，抑制代偿性卵巢肥大，并减少卵巢切除成年雌性大鼠的体重增加。由于o，p '-DDT能够模拟雌激素对这三种神经内分泌反应的作用，因此进行了进一步的实验以确定该化合物是否可以用作研究下丘脑类固醇受体在雌激素刺激生殖行为中的作用的工具。发现单次注射500 mg/kg o，p '-DDT（不诱导性感受性）与下丘脑和垂体中的胞浆雌激素受体相互作用。然而，o，p '-DDT对胞浆受体的消耗非常缓慢且不完全;最大消耗仅为51%，并且直到注射后8小时才发生。还观察到，无论是行为有效还是无效的o，p '-DDT注射都不能诱导下丘脑或垂体中的孕酮受体合成。因此，似乎化合物在单次注射后不能促进脊柱前凸行为可能是由于下丘脑细胞核中受体相互作用不足，但不能诱导神经突触素受体合成不是关键因素。这些数据还表明，研究o，p '-DDT在大脑中的作用可能会提供有用的信息，类固醇介导的神经内分泌反应的机制。
A number of chlorinated insecticides have been shown to interact with estrogen receptors and to mimic estrogen action in peripheral reproductive tissues (e.g. vagina and uterus). The present study was designed to assess whether the dichlorodiphenyltrichloroethane (DDT) isomer o,p'-DDT has estrogenic or antiestrogenic activity in neural estrogen target tissues. Single sc injections of up to 500 mg/kg o,p'-DDT had no effect on female sexual behavior (lordosis). However, more prolonged treatments induced high levels of lordosis behavior, inhibited compensatory ovarian hypertrophy, and reduced body weight gain in ovariectomized adult female rats. Since o,p'-DDT was able to mimic the action of estrogen on these three neuroendocrine responses, further experiments were performed to determine whether the compound could be used as a tool to investigate the role of hypothalamic steroid receptors in estrogen stimulation of reproductive behavior. It was found that single injections of 500 mg/kg o,p'-DDT (which did not induce sexual receptivity) interacted with cytosol estrogen receptors in both the hypothalamus and pituitary. However, depletion of cytosol receptors by o,p'-DDT was very slow and incomplete; maximal depletion was only 51% and did not occur until 8 h postinjection. It was also observed that neither behaviorally effective nor ineffective injections of o,p'-DDT were able to induce progestin receptor synthesis in the hypothalamus or pituitary. Thus, it appears that the inability of the compound to promote lordosis behavior after a single injection probably results from inadequate receptor interaction in hypothalamic cell nuclei, but that failure to induce neural progestin receptor synthesis is not the critical factor. These data also suggest that the study of o,p'-DDT action in the brain may provide useful information regarding mechanisms of steroid mediation of neuroendocrine responses.