Klibanski A, Shupnik M A, Bikkal H A, Black P M, Kliman B, Zervas N T
Thyroid Unit, Massachusetts General Hospital, Boston 02114.
J Clin Endocrinol Metab. 1988 Jan;66(1):96-102. doi: 10.1210/jcem-66-1-96.
Glycoprotein hormone and/or subunit secretion has been increasingly recognized in patients with pituitary nonsecretory adenomas and alpha-subunit secretion has been reported to occur in 5-10% of all pituitary tumors. We investigated the dopaminergic regulation of alpha-subunit secretion in four patients with alpha-subunit secreting pituitary adenomas documented by serum and immunocytochemical studies. In three of the four patients there was a significant decrease in serum alpha-subunit concentrations during 6 weeks of bromocriptine administration. Tumor size decreased in two patients. In pituitary tumor cells from one patient cultured in vitro, dopamine caused a highly significant decrease in media alpha-subunit concentrations. To investigate whether dopaminergic regulation of alpha-subunit secretion occurs at a pre- or posttranslational level, messenger RNA (mRNA) from cultured tumor cells from one patient was analyzed by Northern blot techniques. A decrease in alpha-subunit mRNA occurred in cells incubated with 10(-10), 10(-8), and 10(-6) M dopamine. We conclude that dopamine suppressed pituitary tumor alpha-subunit secretion and mRNA levels. Dopamine agonists may be of benefit in the therapy of patients with such tumors.
垂体无分泌性腺瘤患者中糖蛋白激素和/或亚基分泌越来越受到关注,据报道,所有垂体肿瘤中有5% - 10%会出现α亚基分泌。我们通过血清和免疫细胞化学研究,对4例有α亚基分泌的垂体腺瘤患者的α亚基分泌的多巴胺能调节进行了研究。4例患者中有3例在服用溴隐亭6周期间血清α亚基浓度显著降低。2例患者的肿瘤大小减小。在1例患者的垂体肿瘤细胞体外培养中,多巴胺使培养基中α亚基浓度显著降低。为了研究α亚基分泌的多巴胺能调节是发生在翻译前还是翻译后水平,采用Northern印迹技术分析了1例患者培养的肿瘤细胞中的信使核糖核酸(mRNA)。与10(-10)、10(-8)和10(-6)M多巴胺孵育的细胞中α亚基mRNA减少。我们得出结论,多巴胺抑制垂体肿瘤α亚基分泌和mRNA水平。多巴胺激动剂可能对这类肿瘤患者的治疗有益。