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首页> 外文期刊>Reproductive toxicology >The diverse mechanism of action of dichlorodiphenyldichloroethylene (DDE) and methoxychlor in ovarian cells in vitro.
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The diverse mechanism of action of dichlorodiphenyldichloroethylene (DDE) and methoxychlor in ovarian cells in vitro.

机译：体外二氯二苯基二氯乙烯（DDE）和甲氧基氯在卵巢细胞中的多种作用机理。

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摘要

Dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT), and the DDT analog methoxychlor can have adverse effects on reproduction. These chemicals have been identified as having estrogenic activity. The aim of the current study was to examine the effects of dichlorodiphenyldichloroethylene (DDE), methoxychlor, and estradiol-17beta on steroidogenesis and FSH responsiveness in ovarian cells in vitro. Experiments were performed on a primary culture of porcine granulosa cells and a culture of Chinese hamster ovary (CHO) cells, the latter stably transfected with the FSH receptor (CHO-FSH-R). DDE (10 &mgr;M) and estradiol-17beta (0.1 &mgr;M) but not methoxychlor (10 &mgr;M), increased proliferation of the granulosa cells. DDE (100 and 10 &mgr;M, respectively) decreased FSH-stimulated cAMP synthesis in the granulosa and CHO-FSH-R cells. DDE also decreased progesterone synthesis in the granulosa cells. Methoxychlor (10 &mgr;M) inhibited progesterone synthesis in the granulosa cells, but it did not affect the generation of cAMP in either type of cells studied. However, methoxychlor inhibited estradiol-17beta-stimulated progesterone synthesis in the granulosa cells. We conclude that DDE primarily inhibited the generation of cAMP, while methoxychlor supressed progesterone synthesis through a mechanism distal to cAMP generation. The present results indicate that DDE and methoxychlor are not limited to a mimicking of the endocrine effects of estradiol-17beta in cultured ovarian cells. Therefore, a non-estrogenic component of the endocrine disrupting activities of DDE and methoxychlor must be considered in evaluating their reproductive toxicity.
机译：二氯二苯基二氯乙烯（DDE）是有机氯杀虫剂二氯二苯基三氯乙烷（DDT）中最稳定的代谢产物，以及DDT类似物甲氧基氯可能对繁殖产生不利影响。这些化学物质已被鉴定为具有雌激素活性。本研究的目的是研究二氯二苯基二氯乙烯（DDE），甲氧基氯和雌二醇17beta对体外卵巢细胞中类固醇生成和FSH反应的影响。对猪颗粒细胞的原代培养和中国仓鼠卵巢（CHO）细胞进行了实验，后者被FSH受体（CHO-FSH-R）稳定转染。 DDE（10μM）和雌二醇17beta（0.1μM）而不是甲氧氯（10μM）增强了颗粒细胞的增殖。 DDE（分别为100和10μM）减少了颗粒和CHO-FSH-R细胞中FSH刺激的cAMP合成。 DDE还降低了颗粒细胞中的孕酮合成。甲氧氯（10 mg）可抑制颗粒细胞中的孕酮合成，但在所研究的两种细胞中均不影响cAMP的生成。但是，甲氧氯可抑制颗粒细胞中雌二醇17β刺激的孕酮合成。我们得出的结论是，DDE主要抑制cAMP的生成，而甲氧氯则通过cAMP生成的远端机制抑制了孕酮的合成。目前的结果表明，DDE和甲氧氯不限于模仿培养的卵巢细胞中雌二醇17β的内分泌作用。因此，在评估它们的生殖毒性时，必须考虑DDE和甲氧氯的内分泌干扰活性的非雌激素成分。

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