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. 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.
Pivonello
Rosario
R
Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. rpivone@tin.it
Ferone
Diego
D
de Herder
Wouter W
WW
Kros
Johan M
JM
De Caro
Maria Laura Del Basso
ML
Arvigo
Marica
M
Annunziato
Lucio
L
Lombardi
Gaetano
G
Colao
Annamaria
A
Hofland
Leo J
LJ
Lamberts
Steven W J
SW
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use; D004873:Ergolines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D000324:Adrenocorticotropic Hormone; D000077465:Cabergoline