Heterogenous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas

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 typo 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 mas 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.