Research efforts in the Micevych laboratory involve understanding the cellular and molecular events underlying estrogen action on neurons and glial cells. Estrogen has profound effects on cognitive function and neuroprotection, as well as, reproductive functions. Estrogen affects the expression and activity of various neuropeptides and sex steroids. In particular they have focused on regulation mu-opioid and nociceptin receptors in the CNS regulation of sexual behavior. Recent experiments have demonstrated the synthesis of progesterone in the brain, its regulation by estrogen and physiologic functions of neuroprogesterone. RT-PCR and calcium imaging experiments in neurons and astrocytes have been used to elucidate the mechanisms of estrogen rapid signaling in both glial cells and neurons. The Micevych laboratory has demonstrated that estrogen can modulate nociceptive signaling through rapid actions on primary sensory neurons demonstrating a novel mechanism of estrogen modulation of pain. Additionally, the Micevych Laboratory has been studying the neuroprotective action of estrogen in the nigrostriatal dopamine system. Estrogen activates the insulin-like growth factor-1 (IGF-1) to ameliorate a hallmark of ParkinsonA?s disease A? the neurodegeneration of dopamine neurons. Significantly, estrogen or IGF-1 is efficacious after either central or peripheral administration. Together these experiments underscore the broad range of estrogen signaling influencing both physiology and pathology.