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Dopamine Receptor Expression and Function in Clinically Nonfunctioning Pituitary Tumors: Comparison with the Effectiveness of Cabergoline Treatment

Departments of Molecular and Clinical Endocrinology and Oncology (R.P., M.F., C.D.S., A.C., G.L.); Neuroscience, Section of Pharmacology (R.P., C.M., L.A.); and Neurosurgery (L.M.C., P.C.), "Federico II" University of Naples, Naples 80131, Italy

Address all correspondence and requests for reprints to: Rosario Pivonello, M.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University, Via Sergio Pansini, 5, 80131 Naples, Italy. E-mail: rpivone{at}tin.it.

The aim of this study was to correlate dopamine receptors and D₂ isoform expression with the cabergoline effect on -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 D₂ 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.

D₂ receptor was expressed in 67% of cases. D_2long was found in 50%, D_2short in 17%, and both D₂ isoforms in 33% of cases. D₄ receptor was also expressed in 17% of cases. The in vitro inhibition of -subunit concentration was found in 56% of cases and was associated with D₂ expression (² = 5.6; P < 0.05). After 1 yr of cabergoline treatment, tumor shrinkage was evident in 56% of patients and was associated with D₂ expression (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 D₂ receptor expression and function in nearly 70% of cases, suggesting a role of this drug in the treatment schedule of clinically nonfunctioning pituitary tumors.

Abbreviations: CPSD, Corrected pattern SD; DR, dopamine receptor(s); HPRT, hypoxanthine ribosyl transferase; LiDS, lithium dodecyl sulfate; MD, mean defect; MRI, magnetic resonance imaging; PRL, prolactin; PSD, pattern SD; SF, short-term fluctuation(s).

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