Estradiol-induced enhancement in cell proliferation is mediated through estrogen receptors in the dentate gyrus of adult female rats

High-level estradiol enhances cell proliferation in the dentate gyrus of adult female rats within 4h of administration and then suppresses cell proliferation within 48h via an adrenal steroid-dependent mechanism (Ormerod et al., [2003b] J Neurobiol 55:247-260). Here, we investigate whether the estradiol-induced enhancement in progenitor cell proliferation is mediated through estrogen receptors (ERSs) using the selective ER antagonist ICI 182,780 (10). Ovariectomized Sprague-Dawley rats were given two subcutaneous injections of either vehicle + vehicle (VEH; 0.1 ml sesame oil); VEH+ICl (500 mu g); estradiol benzoate (EB; 10 mu g)+VEH; or EB +ICI. The cell synthesis marker, 5-bromo-2-deoxyuridine (200mg/kg) was administered 4h later. Animals were perfused 24h after BrdU injection and cell proliferation was assessed following immunohistochemical processing of the tissue. Relative to VEH, EB increased cell proliferation by approximately 50%. This EB-induced increase was partially blocked by ICI 182,780 treatment, and ICI 182,780 treatment alone enhanced cell proliferation. Our results demonstrate that estradiol enhances cell proliferation in the dentate gyrus of adult female rats by activating estrogen receptors.