PUBLICATION
Efficacy of pharmacological estrogen receptor antagonist in blocking activation of zebrafish estrogen receptors
- Authors
- Notch, E.G., and Mayer, G.D.
- ID
- ZDB-PUB-110613-6
- Date
- 2011
- Source
- General and comparative endocrinology 173(1): 183-9 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Estradiol/analogs & derivatives
- Estradiol/pharmacology
- Ethinyl Estradiol/pharmacology
- Humans
- Piperidines/pharmacology
- Pyrazoles/pharmacology
- Pyrimidines/pharmacology
- Receptors, Estrogen/agonists
- Receptors, Estrogen/antagonists & inhibitors*
- Receptors, Estrogen/metabolism*
- Selective Estrogen Receptor Modulators/pharmacology
- Zebrafish
- PubMed
- 21641908 Full text @ Gen. Comp. Endocrinol.
Citation
Notch, E.G., and Mayer, G.D. (2011) Efficacy of pharmacological estrogen receptor antagonist in blocking activation of zebrafish estrogen receptors. General and comparative endocrinology. 173(1):183-9.
Abstract
A variety of pharmacological agonists, antagonists and selective estrogen receptor modulators (SERM) have been used to better understand the role of specific receptors in various physiologic processes. Despite similar structure and function, less is known about the effect of agonists and antagonists on teleost estrogen receptors and the results of these studies have indicated wide variation among species. The goal of this study was to determine the ability of two human SERMs to modulate activation of three zebrafish estrogen receptor isoforms. Full length cDNA of zebrafish estrogen receptor 1 (esr1), estrogen receptor 2a (esr2a) and estrogen receptor 2b (esr2b) were cloned into expression vectors and transfected into cells that do not endogenously express any estrogen receptor along with an estrogen responsive luciferase vector. Cells transfected with any of the zebrafish estrogen receptors individually and then exposed to 17β-estradiol (E(2)) or 17α-ethinylestradiol (EE(2)) exhibited a dose dependent increase in luciferase activity. None of the pharmacological antagonists, ICI, methyl-piperidino-pyrazole (MPP) or pyrazolo [1,5-a] pyrimidine (PHTPP), were able to independently transactivate luciferase expression with any of the zebrafish estrogen receptors. Of the three ER antagonists, only ICI 182, 780 was able to block EE(2) induced luciferase activity, although a 10 to 100-fold excess of ICI 182, 780 was necessary with all receptors. Neither MPP nor PHTPP were able to block EE(2) induced luciferase activity with any isoform of zebrafish estrogen receptor. These results indicate that the difference between human ER and zebrafish ER ligand binding is not conserved enough for the SERMs MPP or PHTPP to elicit similar effects in zebrafish as those manifested in humans.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping