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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Estrogenic Actions in the Brain: Estrogen, Phytoestrogens, and Rapid Intracellular Signaling Mechanisms

Scott M. Belcher and Attila Zsarnovszky
Journal of Pharmacology and Experimental Therapeutics November 2001, 299 (2) 408-414;
Scott M. Belcher
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Attila Zsarnovszky
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Abstract

The endogenous gonadal steroid 17β-estradiol (E2) plays an important role in the development, maturation, and function of a wide variety of reproductive and nonreproductive tissues, including those of the nervous system. The actions of E2 at target tissues can be divided into 1) long-term “genomic” actions that are mediated by intracellular estrogen receptor-induced changes in gene expression and 2) rapid actions that modulate a diverse array of intracellular signal transduction cascades. Environmental estrogens are compounds present in the environment that can mimic, and in some cases antagonize, the effects of endogenous estrogens. As a result of these actions, there is currently much interest within the scientific community regarding the relative benefits or threats associated with exposure to different environmental estrogens. Within the general public there is considerable acceptance of the benefits associated with increased use of “natural” estrogens as a component of a healthy diet and in postmenopausal women as an alternative to estrogen replacement therapies. First, this review will focus attention on the role of estrogens in the central nervous system by briefly discussing some of the known mechanisms through which estrogen's effects are mediated, focusing on rapid intracellular signaling mechanisms during neurodevelopment. Second, with the hope of bringing attention to an area of study that until recently has received little consideration, we will briefly discuss phytoestrogens and suggest that these compounds have the potential to influence rapid E2-induced mechanisms in the nervous system in ways that may result in modified brain functions.

Footnotes

  • Abbreviations:
    E2
    estradiol
    ER
    estrogen receptor
    ERE
    estrogen-responsive element
    MAPK
    mitogen-activated protein kinase
    CNS
    central nervous system
    CREB
    cAMP-responsive element binding protein
    ERK
    extracellular regulated kinase
    PKA
    protein kinase A
    PKC
    protein kinase C
    PLC
    phospholipase C
    • Received April 6, 2001.
    • Accepted May 10, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 2
1 Nov 2001
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Estrogenic Actions in the Brain: Estrogen, Phytoestrogens, and Rapid Intracellular Signaling Mechanisms

Scott M. Belcher and Attila Zsarnovszky
Journal of Pharmacology and Experimental Therapeutics November 1, 2001, 299 (2) 408-414;

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Estrogenic Actions in the Brain: Estrogen, Phytoestrogens, and Rapid Intracellular Signaling Mechanisms

Scott M. Belcher and Attila Zsarnovszky
Journal of Pharmacology and Experimental Therapeutics November 1, 2001, 299 (2) 408-414;
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