Kwekkeboom D J, Hofland L J, van Koetsveld P M, Singh R, van den Berge J H, Lamberts S W
Department of Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1990 Sep;71(3):718-24. doi: 10.1210/jcem-71-3-718.
Prolonged treatment with bromocriptine may lead to a decrease in tumor size in patients with a gonadotroph, alpha-subunit-secreting, or clinically nonfunctioning pituitary adenoma. The effectiveness of the treatment, however, may depend on its duration. We investigated the effects of prolonged incubation with bromocriptine on the release and intracellular hormone and alpha-subunit concentrations in 10 such adenomas in vitro. The release of FSH, LH, alpha-subunit, or a combination of these was demonstrated in 7 tumors. Bromocriptine significantly suppressed this release in 6 tumors. In 5 tumors bromocriptine had an inhibitory effect on gonadotropin and/or alpha-subunit release which increased with duration of culture. Withdrawal of bromocriptine during the culture period led to a recovery of gonadotropin or alpha-subunit release in the 2 tumors in which it was tested. Intracellular hormone and alpha-subunit concentrations in 3 of 4 tumors cultured for 4 or more weeks were significantly lower in bromocriptine-treated than in untreated cells. We conclude that 1) bromocriptine can suppress the in vitro release of gonadotropins and alpha-subunit from the majority of clinically nonfunctioning, gonadotroph, and alpha-subunit-secreting pituitary adenomas; 2) during prolonged incubation of these tumors with bromocriptine, this drug has a time-dependent increasing inhibitory effect on the release and synthesis of gonadotropins and alpha-subunit, which eventually may lead to decreased intracellular concentrations of these glycoproteins.
对于促性腺激素分泌型、α亚基分泌型或临床无功能垂体腺瘤患者,长期使用溴隐亭治疗可能会使肿瘤体积缩小。然而,治疗效果可能取决于其持续时间。我们在体外研究了溴隐亭长时间孵育对10例此类腺瘤激素释放以及细胞内激素和α亚基浓度的影响。7例肿瘤显示有促卵泡生成素(FSH)、促黄体生成素(LH)、α亚基或它们的组合释放。溴隐亭显著抑制了6例肿瘤的这种释放。在5例肿瘤中,溴隐亭对促性腺激素和/或α亚基释放有抑制作用,且随着培养时间延长而增强。在培养期间撤除溴隐亭后,在接受测试的2例肿瘤中促性腺激素或α亚基释放恢复。在4例培养4周或更长时间的肿瘤中,3例经溴隐亭处理的肿瘤细胞内激素和α亚基浓度显著低于未处理细胞。我们得出结论:1)溴隐亭可在体外抑制大多数临床无功能、促性腺激素分泌型和α亚基分泌型垂体腺瘤释放促性腺激素和α亚基;2)在这些肿瘤与溴隐亭长时间孵育期间,该药物对促性腺激素和α亚基的释放及合成具有时间依赖性的增强抑制作用,最终可能导致这些糖蛋白的细胞内浓度降低。