Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment.
The aim of this study was to correlate dopamine receptors and D(2) isoform expression with the cabergoline effect on alpha-subunit secretion in vitro and tumor mass in vivo in clinically nonfunctioning pituitary tumors. Eighteen patients were subjected to neurosurgery, and a tumor sample was used for dopamine receptor and D(2) isoform expression evaluation by RT-PCR and the in vitro functional studies. After neurosurgery, nine of 18 patients with persistent tumor were treated with cabergoline and tumor mass was evaluated before and after 1 yr treatment. D(2) receptor was expressed in 67% of cases. D(2long) was found in 50%, D(2short) in 17%, and both D(2) isoforms in 33% of cases. D(4) receptor was also expressed in 17% of cases. The in vitro inhibition of alpha-subunit concentration was found in 56% of cases and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). After 1 yr of cabergoline treatment, tumor shrinkage was evident in 56% of patients and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). The expression of D(2short) rather than D(2long) isoform is associated with the most favorable response of the tumor to cabergoline treatment. In conclusion, this study demonstrates D(2) receptor expression and function in nearly 70% of cases, suggesting a role of this drug in the treatment schedule of clinically nonfunctioning pituitary tumors.
Pivonello
Rosario
R
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy. rpivone@tin.it
Matrone
Carmela
C
Filippella
Mariagiovanna
M
Cavallo
Luigi M
LM
Di Somma
Carolina
C
Cappabianca
Paolo
P
Colao
Annamaria
A
Annunziato
Lucio
L
Lombardi
Gaetano
G
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050638:Receptors, Dopamine D4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014794:Visual Fields / Q000187:drug effects
D000970:Antineoplastic Agents; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D004873:Ergolines; D020033:Protein Isoforms; D021122:Protein Subunits; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D000077465:Cabergoline