Dopamine D2 receptor gene expression in human adenohypophysial adenomas

Abstract

The inhibitory effects of dopamine on adenohypophysial cells are mediated via dopamine subtype 2 receptor (D2R). Dopamine agonists inhibit hormone release and induce tumor shrinkage in most prolactin-secreting adenomas, whereas in other adenoma types such effects are sporadic. We investigated D2R gene expression by in situ hybridization (ISH) and immunocytochemistry in different types of pituitary adenomas. By ISH, a variable D2R signal was detected in 79 of 89 cases: 4 of 6 densely granulated and 8 of 8 sparsely granulated somatotroph, 4 of 4 mammosomatotroph, 7 of 7 mixed somatotroph-lactotroph, 4 of 4 acidophil stem cell, 16 of 16 sparsely granulated lactotroph, 11 of 16 corticotroph (functioning and silent), 3 of 4 silent subtype 3, 5 of 5 thyrotroph, 5 of 6 gonadotroph, 5 of 6 null cell, and 7 of 7 oncocytic adenomas. By immunocytochemistry, D2R protein was localized in cytoplasm and nuclei of 60 of 62 adenomas. In lactotroph adenomas, long-acting bromocriptine (BEC-LAR) induced a major increase in D2R mRNA, which was not accompanied by increased D2R immunoreactivity, suggesting mRNA stabilization. In conclusion, D2R gene is expressed in the majority of pituitary adenomas representing all tumor types. The significance of nuclear localization of D2R protein remains to be clarified.