Related Experiment Videos
Alteration of G alpha subunits mRNA levels in bromocriptine resistant prolactinomas
L Caccavelli1, I Morange-Ramos, C Kordon
1ICNE, CNRS UMR 9941 Université Aix-Marseille II, faculté Médecine Nord, Dramard, Marseille.
Abstract:
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.
Insights
Bromocriptine resistance in prolactinoma patients may stem from reduced dopamine D2 receptors and decreased G alpha i2 protein expression. This impacts treatment effectiveness for many patients.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- Prolactinoma is often treated with bromocriptine, a dopamine D2 receptor agonist.
- Bromocriptine resistance occurs in 5-18% of prolactinomas, linked to lower D2 receptor levels.
- The role of G alpha proteins in bromocriptine resistance is not fully understood.
Purpose of the Study:
- To investigate G alpha protein expression in bromocriptine-resistant prolactinomas.
- To determine if G alpha protein modifications contribute to treatment resistance.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used.
- Compared G alpha protein mRNA levels in sensitive versus resistant prolactinomas.
- Correlated G alpha i2 expression with D2 receptor mRNA and bromocriptine inhibition of prolactin secretion.
Main Results:
- No significant difference in G alpha o or G alpha s mRNA levels was found.
- Relative G alpha i2 expression was significantly decreased in resistant prolactinomas.
- Decreased G alpha i2 expression correlated with reduced D2 receptor mRNA and impaired bromocriptine response.
Conclusions:
- Bromocriptine resistance in prolactinomas may involve decreased D2 receptor density.
- Reduced G alpha i2 protein expression is associated with bromocriptine resistance.
- G alpha i2 may play a role in the mechanism of dopamine D2 receptor signaling in prolactinomas.