Document Detail

Cellular estrogen activity: implications for pulsed estrogen therapy.
MedLine Citation:
PMID:  11390119     Owner:  NLM     Status:  MEDLINE    
Estrogens exert their principal biological effects through the actions of two different intracellular estrogen receptor (ER) proteins, ER alpha and ER beta. Following the binding of steroid, the protein undergoes a conformational change that results in a transcriptionally active form. The receptor protein is locked into an active state by estradiol, which results in the transition of the receptor through a signal transduction cascade of events, ultimately resulting in the activation of specific genes, thereby inducing the biological events specific for that type of target cell. There is a large variation in the relative expression levels of the two ER isoforms in different target tissues and in different stages of development. In addition, variant forms of the two ER isoforms, the result of splice variation, have been described. ER alpha and ER beta have been shown to differ in specific aspects within the various stages of the signal transduction pathway. Thus, there is a broad spectrum of estrogen response mechanisms as a result of an infinite number of possible combinations of all these factors. In addition, there are gene regulatory mechanisms that are the result of ER--protein interactions instead of ER--DNA interactions. Steroid binding is the key initiating action of the whole pathway, which, in terms of cell biology, is a relatively slow process. The response induced through the action of ER induction can be shown to be dependent on the total dose exposure rather than estradiol concentrations at subsaturating levels.
J Carlstedt-Duke
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Maturitas     Volume:  38 Suppl 1     ISSN:  0378-5122     ISO Abbreviation:  Maturitas     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-06     Completed Date:  2001-07-19     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7807333     Medline TA:  Maturitas     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  S7-S13     Citation Subset:  IM    
Department of Medical Nutrition, Karolinska Institutet, Huddinge Hospital, F 60 Novum, SE-141 86 Huddinge, Sweden.
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MeSH Terms
Estrogen Replacement Therapy*
Estrogens / metabolism*
Middle Aged
Protein Isoforms
Receptors, Estrogen / physiology*
Signal Transduction
Reg. No./Substance:
0/Estrogens; 0/Protein Isoforms; 0/Receptors, Estrogen

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