Alteration of G alpha 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.
Caccavelli
L
L
ICNE, CNRS UMR 9941 Université Aix-Marseille II, faculté Médecine Nord, Dramard, Marseille.
Morange-Ramos
I
I
Kordon
C
C
Jaquet
P
P
Enjalbert
A
A
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D001971:Bromocriptine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015175:Prolactinoma / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000096:biosynthesis; D015203:Reproducibility of Results; D014158:Transcription, Genetic
D018491:Dopamine Agonists; D046911:Macromolecular Substances; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go