Schematic at left illustrates our hypothesis that the inhibitory effects of 17β-estradiol (E2) on BV2 cell proliferation and activity may be mediated in part via the sequential metabolism of E2 to 2-hydroxyestradiol (2-OE) and 2-methoxyestradiol (2-ME) by cytochrome P450 (CYP450) and catechol-O-methyltransferase (COMT), respectively. ABT, 1-aminobenzotriazole; PB, phenobarbital; 3-MC, 3-methylcholantherene; OR486, COMT inhibitor. →, Inducer; ⊣, inhibitor. A: effects of increasing concentrations (1–1,000 nmol/l) of E2, 2-OE, and 2-ME on 2.5% FBS-induced DNA synthesis ([3H]thymidine incorporation) by microglia. B: effects of E2, 2-OE, and 2-ME (100 nmol/l) on microglia proliferation (cell no.). Results are presented as means ± SE (n = 4). *P < .05 vs. control (C).