Role of dopamine receptor subtypes DRD2 and DRD5 in drug therapy of pituitary tumors

Abstract

Objective: To study the role of dopamine receptor subtype DRD2 and DRD5 in the treatment of pituitary adenoma, and toprovide a novel strategy for the drug-resistant pituitary adenomas. Methods: Immunohistochemistry was used to detect the expression of dopamine type 5 receptor (DRD5) and dopamine type 2 receptor (DRD2) in 33 primary pituitary tumor tissue samples. Cabergoline, DRD5 agonist (SKF38393),and DRD2 agonist (Quinypirol) were used to treat primary pituitary tumor cells,and MTS was used to evaluate cell activity,in order to analyze the correlation between drug efficacy and the expression of DRD5 and/or DRD2 in 33 pituitary tumor. Results: (1) Pathological analysis of 33 pituitary tμumor tissue samples indicated 17 cases of prolactinoma, 13 cases of non-functional adenoma, 3 cases of growth hormone (GH) tumor,among which 22 cases with high expression of DRD2 (66.7%) and 24 cases with high expression of DRD5 (72.7%). (2) Primary pituitary tumor cells were treated with Cabergoline at 50 μmol/L, Quinypirol at 50 μmol/L and SKF38393 at 25 μmol/L. Among the 33 primary cells,Cabergoline was effective in 25 cases (75.8%),Quinypirol in 16 cases (48.5%),and SKF38393 in 15 cases (45.5%). (3) The efficiency of Cabergoline, Quinypirol and SKF38393 in the primary cell with high expression of DRD2 and DRD5 were78.6%,71.4% and 50% respectively. The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with high DRD2 expression and low DRD5 expression were 75%, 62.5% and 12.5% respectively. The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with low DRD2 expression and high DRD5 expression were 80%, 10% and 70% respectively. The efficiency of Cabergoline, Quinypirol and SKF38393 in the primary cell with low DRD2 and DRD5 expression had no significant activity change. Conclusion: (1) Both DRD2 and DRD5 are highly expressed in pituitary tumors; (2) cabergoline, DRD2 agonist and DRD5 agonist effectively inhibit the growth of pituitary tumor,among which Cabergoline has the highest efficiency; (3) in the absence of DRD2,DRD5 is an alternative target to treat the pituitary tumors.