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Author Hawkins, M. B. ♦ Thomas, P.
Source Paperity
Content type Text
Publisher Oxford University Press
File Format PDF ♦ HTM / HTML
Copyright Year ©2004
Abstract Three forms of estrogen receptor: ERα, ERβ (ERβb), and a second ERβ, ERβa (formerly ERγ) are present in teleost fish. All ERβas share amino acid changes in the ligand binding domain that may influence ligand specificity and receptor function. We compared binding specificities of the three ERs of the teleost fish, Atlantic croaker Micropogonias undulatus. Bacterially expressed Atlantic croaker (ac) ERα, -βb, and -βa fusion proteins showed specific, high affinity binding to 17β-[3H]estradiol, with Kd values of 0.61 ± 0.013, 0.40 ± 0.006, and 0.38 ± 0.059 nm, respectively. Rank orders of binding were: diethylstilbestrol ≫ ICI182780 > 4-hydroxytamoxifen > ICI164384 > estradiol ≥ zearalenone > moxestrol > tamoxifen > estrone ≥ 17α-estradiol > estriol > 2-hydroxyestrone = genistein ≫ RU486 for acERα; ICI182780 > diethylstilbestrol > 4-hydroxytamoxifen > estradiol > ICI164384 > genistein > moxestrol > tamoxifen > zearalenone = estrone > estriol = 17α-estradiol > 2-hydroxyestrone ≫ RU486 for acERβb; and estradiol ≥ diethylstilbestrol > 4-hydroxytamoxifen > ICI182780 > ICI 164384 > estriol ≥ genistein > moxestrol > zearalenone > estrone > 17α-estradiol > RU486 ≥ tamoxifen > 2-hydroxyestrone for acERβa. acERβa showed higher relative binding affinities for estradiol, estriol, and RU486 and lower relative binding affinities for synthetic estrogens and antiestrogens than previously characterized ERs. Mutation of the conserved teleost substitutions (acERβaPhe396) to the ERα or ERβb counterpart shifted diethylstilbestrol and tamoxifen affinities toward those of wild-type acERα and acERβb, supporting the hypothesis that the positions with conserved residue changes in teleost ERs are important to ER structure and function.
Learning Resource Type Article
Publisher Date 2004-06-01
Journal Endocrinology
Volume Number 145
Issue Number 6