Dopamine receptor expression and function in corticotroph pituitary tumors

The role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D-2 receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion and the in vivo effect of short-term cabergoline treatment on cortisol secretion. D2 expression was evaluated by receptor-ligand binding, immunohistochemistry, and RT-PCR. A 50% or more decrease in daily urinary cortisol levels was considered a significant clinical response. At receptor-ligand binding, specific binding of [I-125] epidepride was found in 80% of cases. At immunohistochemistry, specific D-2 immunostaining was found in 75% of cases. D-2 expression was found in 83.3% of cases (D-2long in 40%, D-2short in 20%, and both in 40%) by RT-PCR. Significant in vitro inhibition of ACTH secretion was found in 100% of D-2-positive cases, but not in 100% of D-2-negative cases by either bromocriptine or cabergoline. A significant in vivo inhibition of cortisol secretion after 3-month cabergoline treatment was found in 60%, although a normalization of cortisol secretion was found in 40% of cases. All cabergoline-responsive cases were associated with D-2 expression, whereas all noncabergoline-responsive cases but one were not associated with D-2 expression. In conclusion, functional D-2 receptors were expressed in approximately 80% of corticotroph pituitary tumors. The effectiveness of cabergoline in normalizing cortisol secretion in 40% of cases supports its therapeutic use in the management of Cushing's disease.