Eguchi K, Kawamoto K, Uozumi T, Ito A, Arita K, Kurisu K
Department of Neurosurgery, School of Medicine, Hiroshima University, Japan.
Endocr J. 1995 Apr;42(2):153-61. doi: 10.1507/endocrj.42.153.
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.
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PRL分泌及雌激素诱导的垂体肿瘤的体内作用。对4周龄的Fischer 344大鼠每周皮下注射雌激素，持续10周以诱导肿瘤形成。在雌激素给药的最后一天，以0.6 mg/kg的剂量单次口服或每三天一次长期给予CG或溴隐亭（BC）。在每个治疗方案下采集血清和垂体肿瘤样本。测量血清PRL水平并对垂体称重。通过光学显微镜和电子显微镜进行免疫组织学评估。单次剂量的CG可显著抑制PRL血清水平达6天。单次给予BC后，PRL水平仅在给药后6小时受到显著抑制。与BC相比，持续口服CG在治疗的15至60天内可显著降低血清PRL水平和垂体重量。形态学研究显示，CG可减小细胞和颗粒的大小，并增加细胞质单位面积内的颗粒数量。这些发现表明，CG对PRL分泌颗粒成熟和PRL分泌的抑制作用大于对其合成的抑制作用。因此，CG可使PRL水平长期降低，并对雌激素诱导的大鼠垂体肿瘤具有良好的抗肿瘤作用。
