Much progress has been made during the past year in determining the effects of estrogen in the central nervous system. In addition to its classical action as a transcription factor ligand for the estrogen receptor (ER), there is increasing evidence that estrogen may also act via cross-talk with other signal transduction pathways such as the protein kinase A (PKA) and mitogen activated protein kinase (MAPK) pathways to regulate gene expression in the brain. Another exciting development has been the discovery of a second estrogen receptor, ERβ. Data describing the differential distribution of the estrogen receptors ERα and ERβ in the brain and their varying pharmacological profiles are now being reported. Finally, there is new evidence suggesting that estrogen may have growth factor-like effects or antioxidant activities related to its ability to protect against Alzheimer’s disease. This review will describe the most recent data concerning these diverse actions of estrogen in the central nervous system.
*Department of Psychiatry and Behavioral Sciences, University of Washington, Box 356560, Seattle, WA 98195, USA. †Departments of Psychiatry and Behavioral Sciences and Pharmacology, University of Washington, Seattle, WA, USA.