联合睾酮和雌二醇-17β治疗对雄性大鼠前列腺和肝脏中E2代谢的影响。
Effect of combined testosterone and estradiol-17 beta treatment on the metabolism of E2 in the prostate and liver of noble rats.
作者信息
Lane K E, Ricci M J, Ho S M
机构信息
Department of Biology, Tufts University, Medford, Massachusetts 02155, USA.
出版信息
Prostate. 1997 Mar 1;30(4):256-62. doi: 10.1002/(sici)1097-0045(19970301)30:4<256::aid-pros5>3.0.co;2-j.
BACKGROUND
Long-term treatment of Noble (NBL) rats with testosterone (T) and estradiol-17 beta (E2) induces dysplasia in the dorsolateral lobe (DLP) but not in the ventral lobe (VP) of the rat prostate. The aim of this study was to determine whether metabolic conversion of E2 to catechol estrogens (CEs), which are potentially genotoxic, is a mechanism of estrogen carcinogenicity in this tissue.
METHODS
Male NBL rats were treated simultaneously with T and E2, or left untreated, for 16 weeks after which time the liver, VP, and DLP were excised for microsomal preparations. 3H-E2 metabolites generated in microsomal incubates were separated by high-performance liquid chromatography (HPLC) and identified by coelution with known E2 metabolites.
RESULTS
2- and 4-hydroxyestrogens were detected at high levels in hepatic microsomal incubates, and at extremely low levels in prostatic microsomal incubates. T + E2 treatment of rats did not increase the formation of these prostatic and hepatic metabolites.
CONCLUSIONS
These results do not support CE formation as a mediating step in estrogen-induced tumorigenesis in the rat prostate.
背景
用睾酮（T）和雌二醇-17β（E2）对诺布尔（NBL）大鼠进行长期治疗会在大鼠前列腺的背外侧叶（DLP）诱导发育异常，但不会在腹侧叶（VP）诱导发育异常。本研究的目的是确定E2代谢转化为可能具有遗传毒性的儿茶酚雌激素（CEs）是否是该组织中雌激素致癌作用的一种机制。
方法
雄性NBL大鼠同时接受T和E2治疗，或不接受治疗，持续16周，之后切除肝脏、VP和DLP以制备微粒体。通过高效液相色谱（HPLC）分离微粒体孵育物中产生的3H-E2代谢物，并通过与已知E2代谢物共洗脱进行鉴定。
结果
在肝脏微粒体孵育物中检测到高水平的2-和4-羟基雌激素，而在前列腺微粒体孵育物中检测到极低水平。对大鼠进行T+E2治疗并未增加这些前列腺和肝脏代谢物的形成。
结论
这些结果不支持CE形成作为大鼠前列腺中雌激素诱导肿瘤发生的介导步骤。
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