incubation of cultured bovine adrenal medullary cells with 17 beta-estradiol (E-2) (0.3-100 nM) or membrane-impermeable E-2-bovine serum albumin (100 nM) acutely increased C-14-catecholamine synthesis from [C-14]tyrosine. The stimulatory effect of E-2 was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E-2 also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [H-3]E-2 with apparent K(d)s of 3.2 and 106 nM, and B(max)s of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [H-3]E-2 was most strongly inhibited by E-2 and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E-2 acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla. (c) 2005 Elsevier Inc. All rights reserved.