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Heterogenous Dopamine D2 Receptor Subtype Messenger Ribonucleic Acid Expression in Clinically Nonfunctioning Pituitary Adenomas¹

Max-Planck-Institute of Psychiatry, Clinical Institute, Department of Endocrinology (U.R., U.P., G.K.S.), Munich; Department of Neurology, Technical University of Munich (T.A., S.L., A.W.); Departments of Neurosurgery of the University of Munich (A.M., E.U.) and the Clinic of Mannheim (M.L.), Germany

Address all correspondence and requests for reprints to: Ulrich Renner, Max Planck Institute of Psychiatry, Clinical Institute, Department of Endocrinology, Kraepelinstr. 10, D-80804 Munich, Germany. E-mail: renner{at}mpipsykl.mpg.de

Abstract

Little is known about differences in the expression, localization, and function of the two dopamine D2 receptor subtypes, D2_short and D2_long (D2_s and D2_l), in either normal or adenomatous pituitary. We investigated the messenger RNA (mRNA) expression of the D2 receptor (D2R) subtypes in clinically nonfunctioning pituitary adenomas by in situ hybridization using subtype-specific oligonucleotides. The five normal pituitaries studied expressed similar ratios of D2R subtypes mRNA with a predominant expression of the D2_l isoform. In 2 of 18 clinically inactive adenomas no D2R mRNA was found, whereas in 16 a heterogenous expression of D2R isoforms was observed. Six adenomas expressed only the D2_l and 2 adenomas only the D2_s subtype mRNA; the remaining 8 expressed extremely varying proportions of the two subtypes. The D2R was found only in a subset of the nonfunctioning adenoma cells. In gonadotropin-immunopositive adenomas, the D2R was mainly localized in LH- and FSH-immunopositive cells. Probably because of the heterogenous D2R subtype expression, suppression of cell proliferation was observed in only 3 of 9 adenoma cell cultures in which the growth inhibitory effect of bromocriptine was studied. Although there is some evidence that the presence of the D2_s receptor subtype favors the growth inhibitory response to bromocriptine, further studies with a larger number of inactive adenomas are needed to confirm this speculation.

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