Alteration of Gα Subunits mRNA Levels in Bromocriptine Resistant Prolactinomas

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.