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二甲基苯并(a)蒽诱导的大鼠乳腺肿瘤中的类固醇代谢与类固醇受体

Steroid metabolism and steroid receptors in dimethylbenz(a)anthracene-induced rat mammary tumors.

作者信息

Eechaute W, de Thibault de Boesinghe L, Lacroix E

出版信息

Cancer Res. 1983 Sep;43(9):4260-5.

PMID:6409401
Abstract

Mammary tumors were induced in rats by treatment with dimethylbenz(a)anthracene. Cytosol receptors for 17 beta-estradiol and progesterone were estimated by means of sucrose density gradient centrifugation, and the metabolism of [14C]progesterone, [14C]testosterone, and 17 beta-[14C]estradiol by minced tumor tissue was studied. The estradiol receptor (ER) and progesterone receptor (PR) levels of the tumors varied considerably from less than 5 to 48 fmol/mg protein for ER and to 243 fmol/mg protein for PR. Considering a receptor level lower than 5 fmol/mg protein to be negative, four groups of tumors were found: ER-negative and PR-negative; ER-positive and PR-negative; ER-negative and PR-positive; ER-positive and PR-positive. In dimethylbenz(a)anthracene-induced tumor tissue, high 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase activities and somewhat lower 3 alpha-hydroxysteroid dehydrogenase and 6 alpha-hydroxylase activities were found. No aromatization was detectable. Steroids, especially estradiol, were also metabolized in a high degree to unextractable metabolites. It was concluded that steroid metabolism of dimethylbenz(a)anthracene-induced rat mammary tumors was not related to the ER and/or PR concentration of tumor tissue.

摘要

用二甲基苯并(a)蒽处理大鼠诱发乳腺肿瘤。通过蔗糖密度梯度离心法估算17β-雌二醇和孕酮的胞质受体,并研究切碎的肿瘤组织对[14C]孕酮、[14C]睾酮和17β-[14C]雌二醇的代谢。肿瘤的雌二醇受体(ER)和孕酮受体(PR)水平差异很大,ER从低于5 fmol/mg蛋白质到48 fmol/mg蛋白质不等,PR则高达243 fmol/mg蛋白质。将受体水平低于5 fmol/mg蛋白质视为阴性,发现了四组肿瘤:ER阴性和PR阴性;ER阳性和PR阴性;ER阴性和PR阳性;ER阳性和PR阳性。在二甲基苯并(a)蒽诱导的肿瘤组织中,发现5α-还原酶和20α-羟基类固醇脱氢酶活性较高,而3α-羟基类固醇脱氢酶和6α-羟化酶活性略低。未检测到芳香化作用。类固醇,尤其是雌二醇,也大量代谢为不可提取的代谢产物。得出的结论是,二甲基苯并(a)蒽诱导的大鼠乳腺肿瘤的类固醇代谢与肿瘤组织的ER和/或PR浓度无关。

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