Regulation of striatal dopamine receptors by estrogen

The ability of estrogen to modulate the expression of ventral and dorsal striatal dopamine receptors D(1), D(2,) and D(3) was examined in vivo using semi-quantitative in situ hybridization and ligand binding autoradiography. Two-week treatment with subcutaneous pellets of 17beta-estradiol (25 mg) downregulated D(2) dopamine receptor mRNA in both dorsal and ventral striatum (shell and core regions of nucleus accumbens). No significant changes in D(1) or D(3) mRNA expression were detected. Ligand binding autoradiography did not reveal changes in D(1), D(2,) or D(3) receptor protein expression. We also assessed the ability of 17beta-estradiol to regulate D(2) gene promoter activity in NB41A3 neuroblastoma cells that express this gene endogenously using co-transfections with an estrogen receptor expression vector. While a small fragment of the D(2) promoter could be activated 2.5-fold by estrogen, a larger portion of the D(2) gene was not regulated by this treatment. Estrogens do not appear to have a net effect on striatal dopamine receptor expression. The observed downregulation of D(2) receptor mRNA in the dorsal and ventral striatum in vivo could be secondary to the increased striatal dopamine release induced by estrogen. Synapse 34:222-227, 1999. Published 1999 Wiley-Liss, Inc.