Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting

Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of e...

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Bibliographic Details
Published in:Molecular interventions 2005-12, Vol.5 (6), p.343-357
Main Authors: Hall, Julie M, McDonnell, Donald P
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Animals
Breast Neoplasms - drug therapy
Cell Nucleus - metabolism
Chromatin - metabolism
Estrogen Receptor alpha - agonists
Estrogen Receptor alpha - antagonists & inhibitors
Estrogen Receptor alpha - physiology
Estrogen Receptor beta - agonists
Estrogen Receptor beta - antagonists & inhibitors
Estrogen Receptor beta - physiology
Estrogen Receptor Modulators - pharmacology
Estrogen Receptor Modulators - therapeutic use
Female
Humans
Intracellular Signaling Peptides and Proteins - physiology
Neoplasms, Hormone-Dependent - drug therapy
Repressor Proteins - physiology
Selective Estrogen Receptor Modulators - pharmacology
Signal Transduction
Transcription Factors - physiology
Transcription, Genetic
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Summary:Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of estrogens are mediated through two genetically distinct receptors, ERalpha and ERbeta, which function as hormone-inducible transcription factors. Over the past decade, it has become increasingly clear that the recruitment of coregulatory proteins to ERs is required for ER-mediated transcriptional and biological activities. These "coactivator" complexes enable the ERs to respond appropriately: 1) to hormones or pharmacological ligands, 2) interpret extra- and intra-cellular signals, 3) catalyze the process of chromatin condensation and 4) to communicate with the general transcription apparatus at target gene promoters. In addition to activating proteins, the existence of corepressors, proteins that function as negative regulators of ER activity in either physiological or pharmacological contexts, provides an additional level of complexity in ER action. This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies.
ISSN:1534-0384
1543-2548
DOI:10.1124/mi.5.6.7