EstradiolsS Increases Neuronal Nitric Oxide Synthase via estrogen Receptors in Rat Hippocampus
Estradiol acts directly on hippocampal CA1 pyramidal cells estrogen receptors to increase neuronal nitric oxide (nNOS) and effects of estradiols on nNOS are altered by tamoxifen as an antagonist in the brain. Fetal and neonatal hippocampus of Wistar rats were rapidly removed under general anesthesia. To test role of estrogen in changing NOS activity during gestation, rats at full term received tamoxifen. The rise in fetal NOS activity followed the reported rise in the estrogen receptor concentration in the hippocampus and could be reduced by treatment of the full term with tamoxifen, implicating estrogen in the expression of fetal nNOS activity. The nNOS activity in rat hippocampus did not rise significantly until after birth, richly adult levels approximately two weeks after birth. The appearance of nNOS activity in the rat also followed appearance of estrogen receptors in hippocampus. Thus estrogen receptor in hippocampus results in increased nNOS activity. Thus, increased NO production by nNOS may contribute to the neuroprotective effects of estrogen.