ALTERATION OF G-ALPHA SUBUNITS MESSENGER-RNA LEVELS IN BROMOCRIPTINE RESISTANT PROLACTINOMAS

Patients with prolactinoma are commonly treated with the D2 dopamine a gonist 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 D 2 receptor density and mRNA levels, In this study, we used quantitativ e RT-PCR to investigate whether expression of G alpha proteins could b e also modified in bromocriptine resistant prolactinomas, No differenc e in G alpha o mRNA levels or in the relative expression of G alpha s between bromocriptine sensitive and bromocriptine resistant prolactino mas was observed, In contrast, the relative expression of G alpha i(2) was found to be decreased in bromocriptine resistant prolactinomas wh en compared to that of bromocriptine sensitive prolactinomas, Interest ingly, the relative G alpha i(2) expression was correlated to both bro mocriptine inhibition of in vitro PRL secretion and D2 receptor mRNA l evels, Bromocriptine resistance could thus result from a decrease in D 2 dopamine receptors associated with a decrease in G alpha i(2) expres sion.