Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms.
- 1 December 2001
- journal article
- review article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 91 (6), 2785-2801
- https://doi.org/10.1152/jappl.2001.91.6.2785
Abstract
Besides their well-established actions on reproductive functions, estrogens exert a variety of actions on many regions of the nervous system that influence higher cognitive function, pain mechanisms, fine motor skills, mood, and susceptibility to seizures; they also appear to have neuroprotective actions in relation to stroke damage and Alzheimer's disease. Estrogen actions are now recognized to occur via two different intracellular estrogen receptors, ER-alpha and ER-beta, that reside in the cell nuclei of some nerve cells, as well as by some less well-characterized mechanisms. In the hippocampus, such nerve cells are sparse in number and yet appear to exert a powerful influence on synapse formation by neurons that do not have high levels of nuclear estrogen receptors. However, we also find nonnuclear estrogen receptors outside of the cell nuclei in dendrites, presynaptic terminals, and glial cells, where estrogen receptors may couple to second messenger systems to regulate a variety of cellular events and signal to the nuclear via transcriptional regulators such as CREB. Sex differences exist in many of the actions of estrogens in the brain, and the process of sexual differentiation appears to affect many brain regions outside of the traditional brain areas involved in reproductive functions. Finally, the aging brain is responsive to actions of estrogens, which have neuroprotective effects both in vivo and in vitro. However, in an animal model, the actions of estrogens on the hippocampus appear to be somewhat attenuated with age. In the future, estrogen actions over puberty and in pregnancy and lactation should be further explored and should be studied in both the hypothalamus and the extrahypothalamic regions.Keywords
This publication has 99 references indexed in Scilit:
- Localization of estrogen receptor alpha (ERα) in pyramidal neurons of the developing rat hippocampusDevelopmental Brain Research, 2001
- Expression of estrogen receptor-beta protein and mRNA in the cerebellum of the ratNeuroscience Letters, 2000
- Regulated expression of estrogen receptor α and β mRNA in granule cells during development of the rat cerebellumDevelopmental Brain Research, 1999
- A Novel Isoform of Rat Estrogen Receptor Beta with 18 Amino Acid Insertion in the Ligand Binding Domain as a Putative Dominant Negative Regulator of Estrogen ActionBiochemical and Biophysical Research Communications, 1998
- Molecular Characterization of the Dendritic Growth Cone: Regulated mRNA Transport and Local Protein SynthesisNeuron, 1996
- The hippocampus—what does it do?Behavioral and Neural Biology, 1992
- Transient elevation of estrogen receptors in the neonatal rat hippocampusDevelopmental Brain Research, 1990
- Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesiclesCell, 1985
- Perinatal development of hypothalamic and cortical estrogen receptors in mouse brain: Methodological aspectsDevelopmental Brain Research, 1983
- Steroid hormone target sites in the brain: The differential distribution of estrogen, progestin, androgen and glucocorticosteroidJournal of Steroid Biochemistry, 1976