Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma development in rats.
Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma development in rats.
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DOI：
10.1262/jrd.20026
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发表时间：
2009-04
期刊：
影响因子：
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通讯作者：
Midori Yoshida;G. Watanabe;Tomo Suzuki;Kaoru Inoue;Miwa Takahashi;A. Maekawa;K. Taya;A. Nishikawa
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文献类型：
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作者：
Midori Yoshida;G. Watanabe;Tomo Suzuki;Kaoru Inoue;Miwa Takahashi;A. Maekawa;K. Taya;A. Nishikawa
使用大鼠子宫癌模型研究了溴隐亭（BRC）治疗长期阻断催乳素（PRL）作用对子宫癌发生和相关卵巢生理学的影响。子宫体肿瘤（子宫内膜腺癌）高产品系10周龄雌性Donryu大鼠，以N-乙基-N'-硝基-N-亚硝基胍（ENNG）作为肿瘤引发剂，每周皮下注射1 mg/kg体重4次直至14.5月龄，以阻断发情前期PRL激增。该研究在15月龄时终止，结果显示，长期BRC治疗在发病率（34.6%至13.0%，5%时显着差异）和复数（0.35至0.18，5%时显着差异）（表示每只动物的腺癌数量）方面均显着抑制子宫内膜腺癌的发展。虽然BRC不影响治疗动物的动情周期，但血清17β-雌二醇（E2）与黄体酮（P）比率（E：P比率）明显下降，并且血清E2水平在15月龄时呈现下降趋势。虽然无法确定产生抑制作用的确切途径；卵巢激素失衡降低血清 E:P 比率的途径很可能发挥着至关重要的作用。
The effects of long-term blockade of prolactin (PRL) action by bromocriptine (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu rats, a high yield strain for uterine corpus tumors (endometrial adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4 times per week until 14.5 months of age to block the proestrus PRL surge. The study was terminated at 15 months of age, and the results showed that long-term BRC treatment significantly inhibited endometrial adenocarcinoma development in terms of both incidence (34.6% to 13.0% with significant difference at 5%) and multiplicity (0.35 to 0.18 with significant difference at 5%), which indicates the number of adenocarcinomas per animals. While BRC did not affect estrous cyclicity in the treated animals, a significant decline was evident in the serum 17 beta-estradiol (E2) to progesterone (P) ratio (E: P ratio), and the serum E2 level showed a decreased tendency at 15 months of age. While the precise pathway to the inhibitory effect could not be determined; the pathway by which ovarian hormonal imbalance decreases the serum E: P ratio most likely plays a crucial role.