Estrogen Effects and Mechanism of Action in the Central Nervous System

Joe, Sook Haeng; Kim, Jung Woong

Abstract

Estrogens have diverse effects on the CNS throughout the lifespan and do so via multiple mechanisms involving both genomic and non-genomic receptors. Estrogens affect not only the hypothalamus but also catecholamine, serotonin, acetylcholine and dopamine system including hippocampus, nigrostriatal, and glial cells. These systems are involved in a variety of estrogen actions on mood, locomotor activity, pain sensitivity, and cognition. Estrogens act primarily by classic genomic mechanisms through intracellular receptors to modulate transcription and protein synthesis. Estrogens also act via second messenger such as cAMP regulation, MAP kinase regulation and calcium homeostasis. These actions may be related to non-genomic receptors, the membrane-binding receptors, which are not well identified. Furthermore estrogens act as potent neuroprotective and neurotrophic factors by estrogen receptor dependent and independent mechanisms. There are some supports that estrogens are helpful for mood disturbance in reproductive-related conditions. Also inconsistent effects of estrogens on mood and cognitive functions associated with the postmenopause, Alzheimer's disease, and neurotrauma are reported. Based upon diversity of region and molecular mechanism of action of estrogens in the brain, much more research is required to establish guideline for using estrogen as a potential antidepressant, cognitive enhancer, and neuroprotective agent in the clinical practice of psychiatry.