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. D(2) 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 [(125)I]
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.