BIOCHEMICAL-ALTERATIONS IN SEX HORMONE-INDUCED HYPERPLASIA AND DYSPLASIA OF THE DORSOLATERAL PROSTATES OF NOBLE RATS
BIOCHEMICAL-ALTERATIONS IN SEX HORMONE-INDUCED HYPERPLASIA AND DYSPLASIA OF THE DORSOLATERAL PROSTATES OF NOBLE RATS
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DOI：
10.1093/jnci/80.13.1045
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发表时间：
1988-09-07
影响因子：
10.3
通讯作者：
DAMASSA, D
中科院分区：
文献类型：
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作者：
LEAV, I;HO, SM;DAMASSA, D
用睾酮和17 β-雌二醇同时植入完整的Noble（Nb）大鼠雌二醇（E2）填充的硅橡胶胶囊16周引起所有动物的背外侧前列腺（DLP）的非典型增生（发育不良）和显著增大。异型增生病变可能是肿瘤前病变，因为已知Nb大鼠长期给予这些类固醇可诱导DLP中腺癌的高发生率。用非芳香化的5 α-双氢睾酮（DHT）治疗16周引起的扩大，但不发育不良，暗示雌激素作为一个关键因素的发生增生性病变。与对照组相比，睾酮加E2治疗导致核II型雌激素结合位点增加2.5倍，仅限于DLP。两种治疗均未显著改变腹侧前列腺或DLP中的雄激素含量或雄激素受体水平。含有发育异常病灶的扩大DLP的器官培养物比对照组织代谢更多的[3 H]DHT，这导致5 α-DHD的形成增加。雄甾烷-3 β，17. β-二醇（3 β-雄甾烷）代谢产物。因为3.beta雄甾烷素先前已显示从胞质I型雌激素结合位点置换[3 H]E2，发育异常可能是由激素及其以异常量产生的正常代谢物过度刺激DLP引起的。
Simultaneous implantation of intact Noble (Nb) rats with testosterone and 17.beta.-estradiol (E2)-filled silastic capsules for 16 weeks caused atypical hyperplasia (dysplasia) and striking enlargement exclusively in the dorsolateral prostates (DLPs) of all animals. The dysplastic lesion may be preneoplastic since long-term administration of these steroids to Nb rats is known to induce a high incidence of adenocarcinoma in the DLP. Treatment of rats with nonaromatizable 5.alpha.-dihydrotestosterone (DHT) for 16 weeks caused enlargement but not dysplasia, implicating estrogen as a key factor in the genesis of the proliferative lesion. Compared with controls, the testosterone plus E2 treatment caused a 2.5-fold increase in nuclear type II estrogen binding sites which were confined to the DLP. Neither treatment significantly altered androgen content or levels of androgen receptor in the ventral prostate or DLP. Organ cultures of enlarged DLP containing foci of dysplasia metabolized more [3H]DHT than control tissue, which resulted in increased formation of the 5.alpha.-androstane-3.beta., 17.beta.-diol (3.beta.-androstanediol) metabolite by these explants. Because 3.beta.-androstanediol has previously been shown to displace [3H]E2 from cytosolic type I estrogen binding sites, the dysplasia may be caused by hyperstimulation of the DLP by the hormones and their normal metabolites produced in abnormal amounts.