help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on June 9, 2005
Endocrinology, doi:10.1210/en.2004-1616
A more recent version of this article appeared on September 1, 2005
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
146/9/3843    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Toran-Allerand, C. D.
Right arrow Articles by Nethrapalli, I. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toran-Allerand, C. D.
Right arrow Articles by Nethrapalli, I. S.

Submitted on December 15, 2004
Accepted on May 27, 2005

17{alpha}-ESTRADIOL: A BRAIN ACTIVE ESTROGEN?

C. Dominique Toran-Allerand*, Alexander A. Tinnikov, Ravinder J. Singh, and Imam S. Nethrapalli

Departments of Anatomy & Cell Biology, Obstetrics & Gynecology, (C.D.T-A., A.A.T., I.S.N.) and Neurology (C.D.T-A.) and the Centers for Neurobiology and Behavior and Reproductive Sciences (C.D.T-A., A.A.T., I.S.N.), Columbia University College of Physicians & Surgeons, New York, New York 10032, and Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation (R.J.S.), Rochester, MN 55905, U.S.A.

* To whom correspondence should be addressed. E-mail: cdt2{at}columbia.edu.

The estrogen 17{beta}-estradiol has profound effects on the brain throughout life, while 17{alpha}-estradiol, the natural optical isomer, is generally considered less active, because it binds less avidly to estrogen receptors. On the contrary, recent studies in the brain document that 17{alpha}-estradiol (a) elicits rapid and sustained activation of the MAP/ERK kinase and PI3K-Akt signaling pathways, (b) is neuroprotective, following an ischemic stroke and oxidative stress, and in transgenic mice with Alzheimer's disease, and (c) influences spatial memory and hippocampal-dependent synaptic plasticity. The present study measured the endogenous content of 17{alpha}-estradiol in the brain and further clarified its actions and kinetics. Here we report that (i) endogenous levels of 17{alpha}-estradiol and its precursor estrone are significantly elevated in the postnatal and adult mouse brain and adrenal gland of both sexes, as determined by liquid chromatography/tandem mass spectrometry (LC-MS/MS); (ii) 17{alpha}-estradiol and 17{beta}-estradiol bind estrogen receptors with similar binding affinities; (iii) 17{alpha}-estradiol transactivates an estrogen-responsive reporter gene, and (iv) unlike 17{beta}-estradiol, 17{alpha}-estradiol does not bind {alpha}-fetoprotein or sex hormone binding globulin, the estrogen-binding plasma proteins of the developing rodent and primate, respectively. 17{alpha}-estradiol was also found in the brains of gonadectomized or gonadectomized/adrenalectomized mice, supporting the hypothesis that 17{alpha}-estradiol is locally synthesized in the brain. These findings challenge the view that 17{alpha}-estradiol is without biological significance and suggest that 17{alpha}-estradiol and its selective receptor "ER-X" are not part of a classical hormone/receptor endocrine system, but of a system with important autocrine/paracrine functions in the developing and adult brain. 17{alpha}-estradiol may have enormous implications for hormone replacement strategies at the menopause and in the treatment of such neurodegenerative disorders as Alzheimer's disease and ischemic stroke.
Key words: 17{alpha}-estradiol • 17{beta}-estradiol • estrone • "ER-X" • brain • liquid chromatography-tandem mass spectrometry




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
M. M. McCARTHY
Estradiol and the Developing Brain
Physiol Rev, January 1, 2008; 88(1): 91 - 134.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. M. Wang, L. Liu, and R. D. Brinton
Estradiol-17 -Induced Human Neural Progenitor Cell Proliferation Is Mediated by an Estrogen Receptor -Phosphorylated Extracellularly Regulated Kinase Pathway
Endocrinology, January 1, 2008; 149(1): 208 - 218.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Fournier, M. Allard, R. Gulemetova, V. Joseph, and R. Kinkead
Chronic corticosterone elevation and sex-specific augmentation of the hypoxic ventilatory response in awake rats
J. Physiol., November 1, 2007; 584(3): 951 - 962.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Meffre, A. Pianos, P. Liere, B. Eychenne, A. Cambourg, M. Schumacher, D. G. Stein, and R. Guennoun
Steroid Profiling in Brain and Plasma of Male and Pseudopregnant Female Rats after Traumatic Brain Injury: Analysis by Gas Chromatography/Mass Spectrometry
Endocrinology, May 1, 2007; 148(5): 2505 - 2517.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Musatov, W. Chen, D. W. Pfaff, C. V. Mobbs, X.-J. Yang, D. J. Clegg, M. G. Kaplitt, and S. Ogawa
Silencing of estrogen receptor {alpha} in the ventromedial nucleus of hypothalamus leads to metabolic syndrome
PNAS, February 13, 2007; 104(7): 2501 - 2506.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Mannella and R. D. Brinton
Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action.
J. Neurosci., September 13, 2006; 26(37): 9439 - 9447.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society