IN-VIVO EFFECT OF CABERGOLINE, A DOPAMINE AGONIST, ON ESTROGEN-INDUCED RAT PITUITARY-TUMORS
IN-VIVO EFFECT OF CABERGOLINE, A DOPAMINE AGONIST, ON ESTROGEN-INDUCED RAT PITUITARY-TUMORS
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DOI：
10.1507/endocrj.42.153
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发表时间：
1995-04-01
影响因子：
2
通讯作者：
KURISU, K
中科院分区：
文献类型：
--
作者：
EGUCHI, K;KAWAMOTO, K;KURISU, K
卡麦角林（CG）是一种多巴胺激动剂，可抑制催乳素（PRL）和生长激素的分泌。在本研究中，我们评估了CG对催乳素分泌和雌激素诱导的垂体瘤的体内影响。雌激素通过皮下注射给予4周龄Fischer 344大鼠，每周一次，持续10周，以诱导肿瘤。在雌激素给药的最后一天，CG或溴隐亭（BC）的剂量为0.6 mg/kg，以单次口服途径给药或每三天一次长期给药。在每个给药方案中采集血清和垂体肿瘤样本。测定血清PRL水平并称重垂体。通过光学显微镜和电子显微镜进行免疫组织学评价。单剂量CG可显著抑制血清PRL水平，持续6天。BC单次给药后，仅在给药后6 h才显著抑制PRL水平。连续口服CG 15 ~ 60天，血清PRL水平和垂体重量均显著低于BC。形态学研究表明，CG减少了细胞和颗粒的大小，并增加了每单位面积的细胞质颗粒的数量。这些结果表明，CG抑制PRL分泌颗粒的成熟和PRL的分泌超过其合成。因此，CG诱导PRL的长期降低，对雌激素诱导的大鼠垂体瘤有良好的抗肿瘤作用。
Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin (PRL) and growth hormone. In the present study, we evaluated the in vivo effect of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for 10 weeks to induce tumors. On the last day of estrogen administration, doses of either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral route or chronically, given every third day. Sera and pituitary tumors were sampled on each treatment schedule. Serum levels of PRL were measured and the pituitary glands were weighed. Immunohistological evaluation was performed by optical and electron microscopy. A single dose of CG significantly inhibited the serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was significantly inhibited only at 6 hours' postadministration. The continued oral administration of CG significantly reduced both the serum PRL level and the weight of the pituitary during 15 to 60 days of treatment as compared with BC. Morphologic studies revealed that CG reduced the size of the cells and of the granules, and increased the number of granules per unit area of the cytoplasm. These findings suggest that CG inhibits the maturation of PRL secretory granules and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen.