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Non-genomic actions of estrogens and their interaction with genomic actions in the brain

Vasudevan, N. and Pfaff, D. W. (2008) Non-genomic actions of estrogens and their interaction with genomic actions in the brain. Frontiers in Neuroendocrinology, 29 (2). pp. 238-57. ISSN 1095-6808

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To link to this item DOI: 10.1016/j.yfrne.2007.08.003

Abstract/Summary

Ligands for the nuclear receptor superfamily have at least two mechanisms of action: (a) classical transcriptional regulation of target genes (genomic mechanisms); and (b) non-genomic actions, which are initiated at the cell membrane, which could also impact transcription. Though transcriptional mechanisms are increasingly well understood, membrane-initiated actions of these ligands are incompletely understood. This has led to considerable debate over the physiological relevance of membrane-initiated actions of hormones versus genomic actions of hormones, with genomic actions predominating in the endocrine field. There is good evidence that the membrane-limited actions of hormones, particularly estrogens, involve the rapid activation of kinases and the release of calcium and that these are linked to physiologically relevant scenarios in the brain. We show evidence in this review, that membrane actions of estrogens, which activate these rapid signaling cascades, can also potentiate nuclear transcription in both the central nervous system and in non-neuronal cell lines. We present a theoretical scenario which can be used to understand this phenomenon. These signaling cascades may occur in parallel or in series but subsequently, converge at the modification of transcriptionally relevant molecules such as nuclear receptors and/or coactivators. In addition, other non-cognate hormones or neurotransmitters may also activate cascades to crosstalk with estrogen receptor-mediated transcription, though the relevance of this is less clear. The idea that coupling between membrane-initiated and genomic actions of hormones is a novel idea in neuroendocrinology and provides us with a unified view of hormone action in the central nervous system.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
ID Code:58932
Uncontrolled Keywords:Animals Brain/*metabolism Cell Line, Tumor Estradiol/pharmacology Estrogens/*physiology Female Genome Humans Mitogen-Activated Protein Kinases/physiology Models, Biological Neurons/drug effects/physiology Ovariectomy Phosphorylation Receptors, Cell Surface/physiology Receptors, Estrogen/*physiology Signal Transduction/physiology Transcription, Genetic/drug effects

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