Caccavelli L, Morange-Ramos I, Kordon C, Jaquet P, Enjalbert A
ICNE, CNRS UMR 9941 Université Aix-Marseille II, faculté Médecine Nord, Dramard, Marseille.
J Neuroendocrinol. 1996 Oct;8(10):737-46. doi: 10.1046/j.1365-2826.1996.04902.x.
Patients with prolactinoma are commonly treated with the D2 dopamine agonist bromocriptine, which in most cases, normalizes prolactin (PRL) levels. However, resistance to bromocriptine has been observed in 5 to 18% of tested prolactinomas and is associated to a decrease in both D2 receptor density and mRNA levels. In this study, we used quantitative RT-PCR to investigate whether expression of G alpha proteins could be also modified in bromocriptine resistant prolactinomas. No difference in G alpha o mRNA levels or in the relative expression of G alpha s between bromocriptine sensitive and bromocriptine resistant prolactinomas was observed. In contrast, the relative expression of G alpha i2 was found to be decreased in bromocriptine resistant prolactinomas when compared to that of bromocriptine sensitive prolactinomas. Interestingly, the relative G alpha i2 expression was correlated to both bromocriptine inhibition of in vitro PRL secretion and D2 receptor mRNA levels. Bromocriptine resistance could thus result from a decrease in D2 dopamine receptors associated with a decrease in G alpha i2 expression.
催乳素瘤患者通常用D2多巴胺激动剂溴隐亭治疗，在大多数情况下，溴隐亭可使催乳素（PRL）水平恢复正常。然而，在5%至18%的受试催乳素瘤中观察到对溴隐亭的耐药性，这与D2受体密度和mRNA水平的降低有关。在本研究中，我们使用定量逆转录聚合酶链反应（RT-PCR）来研究在对溴隐亭耐药的催乳素瘤中Gα蛋白的表达是否也会发生改变。在对溴隐亭敏感和耐药的催乳素瘤之间，未观察到Gαo mRNA水平或Gαs相对表达的差异。相比之下，与对溴隐亭敏感的催乳素瘤相比，在对溴隐亭耐药的催乳素瘤中发现Gαi2的相对表达降低。有趣的是，Gαi2的相对表达与溴隐亭对体外PRL分泌的抑制作用以及D2受体mRNA水平均相关。因此，溴隐亭耐药可能是由于D2多巴胺受体减少以及Gαi2表达降低所致。
