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and ERß Expressed in Chinese Hamster Ovary Cells
Division of Endocrinology (E.R.L.) Long Beach Veterans Affairs
Medical Center Long Beach, California 90822
Departments
of Medicine (M.R., A.P., E.R.L.) and Pharmacology (E.R.L.)
University of California, Irvine Irvine, California 92717
The Ben May Institute (G.L.G.) University of Chicago
Chicago, Illinois 60637
The existence of a putative membrane estrogen
receptor (ER) has been supported by studies accomplished over the past
20 yr. However, the origin and functions of this receptor are not well
defined. To study the membrane receptor, we transiently transfected
cDNAs for ER
or ERß into Chinese hamster ovary (CHO) cells.
Transfection of ER resulted in a single transcript by Northern blot,
specific binding of labeled 17ß-estradiol
(E2), and expression of ER in both nuclear and
membrane cell fractions. Competitive binding studies in both
compartments revealed near identical dissociation constants
(Kds) of 0.283 and 0.287
nM, respectively, but the membrane receptor
number was only 3% as great as the nuclear receptor density.
Transfection of ERß also yielded a single transcript and nuclear and
membrane receptors with respective Kd values of
1.23 and 1.14 nM; the membrane receptor number
was only 2% compared with expressed nuclear receptors. Estradiol
binding to CHO-ER or CHO-ERß activated Gq and Gs proteins in
the membrane and rapidly stimulated corresponding inositol phosphate
production and adenylate cyclase activity. Binding by
17-ß-E2 to either expressed receptor
comparably enhanced the nuclear incorporation of thymidine, critically
dependent upon the activation of the mitogen-activated protein
kinase, ERK (extracellular regulated kinase). In contrast, c-Jun
N-terminal kinase activity was stimulated by
17-ß-E2 in ERß-expressing CHO, but was
inhibited in CHO-ER cells. In summary, membrane and nuclear ER can
be derived from a single transcript and have near-identical affinities
for 17-ß-E2, but there are considerably more
nuclear than membrane receptors. This is also the first report that
cells can express a membrane ERß. Both membrane ERs activate G
proteins, ERK, and cell proliferation, but there is novel differential
regulation of c-Jun kinase activity by ERß and ER.
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J. S Lewis, T J Thomas, R. G Pestell, C. Albanese, M. A Gallo, and T. Thomas Differential effects of 16{alpha}-hydroxyestrone and 2-methoxyestradiol on cyclin D1 involving the transcription factor ATF-2 in MCF-7 breast cancer cells J. Mol. Endocrinol., February 1, 2005; 34(1): 91 - 105. [Abstract] [Full Text] [PDF]
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J. L. Temple and S. Wray Bovine Serum Albumin-Estrogen Compounds Differentially Alter Gonadotropin-Releasing Hormone-1 Neuronal Activity Endocrinology, February 1, 2005; 146(2): 558 - 563. [Abstract] [Full Text] [PDF]
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P. Thomas, Y. Pang, E. J. Filardo, and J. Dong Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells Endocrinology, February 1, 2005; 146(2): 624 - 632. [Abstract] [Full Text] [PDF]
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 A. M. Tarrant Endocrine-like Signaling in Cnidarians: Current Understanding and Implications for Ecophysiology Integr. Comp. Biol., January 1, 2005; 45(1): 201 - 214. [Abstract] [Full Text] [PDF]
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I. S. Nethrapalli, A. A. Tinnikov, V. Krishnan, C. D. Lei, and C. D. Toran-Allerand Estrogen Activates Mitogen-Activated Protein Kinase in Native, Nontransfected CHO-K1, COS-7, and RAT2 Fibroblast Cell Lines Endocrinology, January 1, 2005; 146(1): 56 - 63. [Abstract] [Full Text] [PDF]
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 F. Acconcia, P. Ascenzi, A. Bocedi, E. Spisni, V. Tomasi, A. Trentalance, P. Visca, and M. Marino Palmitoylation-dependent Estrogen Receptor {alpha} Membrane Localization: Regulation by 17{beta}-Estradiol Mol. Biol. Cell, January 1, 2005; 16(1): 231 - 237. [Abstract] [Full Text] [PDF]
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M. Razandi, A. Pedram, I. Merchenthaler, G. L. Greene, and E. R. Levin Plasma Membrane Estrogen Receptors Exist and Functions as Dimers Mol. Endocrinol., December 1, 2004; 18(12): 2854 - 2865. [Abstract] [Full Text] [PDF]
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E. Unni, S. Sun, B. Nan, M. J. McPhaul, B. Cheskis, M. A. Mancini, and M. Marcelli Changes in Androgen Receptor Nongenotropic Signaling Correlate with Transition of LNCaP Cells to Androgen Independence Cancer Res., October 1, 2004; 64(19): 7156 - 7168. [Abstract] [Full Text] [PDF]
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L.-M. Kow and D. W. Pfaff The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions PNAS, August 17, 2004; 101(33): 12354 - 12357. [Abstract] [Full Text] [PDF]
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 L. H. Smith, S. R. Coats, H. Qin, M. S. Petrie, J. W. Covington, M. Su, M. Eren, and D. E. Vaughan Differential and Opposing Regulation of PAI-1 Promoter Activity by Estrogen Receptor {alpha} and Estrogen Receptor {beta} in Endothelial Cells Circ. Res., August 6, 2004; 95(3): 269 - 275. [Abstract] [Full Text] [PDF]
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V. V. Chaban, A. J. Lakhter, and P. Micevych A Membrane Estrogen Receptor Mediates Intracellular Calcium Release in Astrocytes Endocrinology, August 1, 2004; 145(8): 3788 - 3795. [Abstract] [Full Text] [PDF]
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J. L. Temple, E. Laing, A. Sunder, and S. Wray Direct Action of Estradiol on Gonadotropin-Releasing Hormone-1 Neuronal Activity via a Transcription-Dependent Mechanism J. Neurosci., July 14, 2004; 24(28): 6326 - 6333. [Abstract] [Full Text] [PDF]
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M. M. McCarthy Out with the New, in with the Old: Classical Estrogen Receptors Mediate Novel Estradiol Actions in Brain Endocrinology, July 1, 2004; 145(7): 3053 - 3054. [Full Text] [PDF]
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I. M. Abraham, M. G. Todman, K. S. Korach, and A. E. Herbison Critical in Vivo Roles for Classical Estrogen Receptors in Rapid Estrogen Actions on Intracellular Signaling in Mouse Brain Endocrinology, July 1, 2004; 145(7): 3055 - 3061. [Abstract] [Full Text] [PDF]
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A. M. Braun and P. Thomas Biochemical Characterization of a Membrane Androgen Receptor in the Ovary of the Atlantic Croaker (Micropogonias undulatus) Biol Reprod, July 1, 2004; 71(1): 146 - 155. [Abstract] [Full Text] [PDF]
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O. Kretz, L. Fester, U. Wehrenberg, L. Zhou, S. Brauckmann, S. Zhao, J. Prange-Kiel, T. Naumann, H. Jarry, M. Frotscher, et al. Hippocampal Synapses Depend on Hippocampal Estrogen Synthesis J. Neurosci., June 30, 2004; 24(26): 5913 - 5921. [Abstract] [Full Text] [PDF]
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M. Maggiolini, A. Vivacqua, G. Fasanella, A. G. Recchia, D. Sisci, V. Pezzi, D. Montanaro, A. M. Musti, D. Picard, and S. Ando The G Protein-coupled Receptor GPR30 Mediates c-fos Up-regulation by 17{beta}-Estradiol and Phytoestrogens in Breast Cancer Cells J. Biol. Chem., June 25, 2004; 279(26): 27008 - 27016. [Abstract] [Full Text] [PDF]
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 J. Q. Chen, M. Delannoy, C. Cooke, and J. D. Yager Mitochondrial localization of ER{alpha} and ER{beta} in human MCF7 cells Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E1011 - E1022. [Abstract] [Full Text] [PDF]
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F. Barletta, C.-W. Wong, C. McNally, B. S. Komm, B. Katzenellenbogen, and B. J. Cheskis Characterization of the Interactions of Estrogen Receptor and MNAR in the Activation of cSrc Mol. Endocrinol., May 1, 2004; 18(5): 1096 - 1108. [Abstract] [Full Text] [PDF]
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J. D. Blaustein Minireview: Neuronal Steroid Hormone Receptors: They're Not Just for Hormones Anymore Endocrinology, March 1, 2004; 145(3): 1075 - 1081. [Abstract] [Full Text] [PDF]
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C. D. Toran-Allerand Minireview: A Plethora of Estrogen Receptors in the Brain: Where Will It End? Endocrinology, March 1, 2004; 145(3): 1069 - 1074. [Abstract] [Full Text] [PDF]
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Y. Xu, R. J. Traystman, P. D. Hurn, and M. M. Wang Membrane Restraint of Estrogen Receptor {alpha} Enhances Estrogen-Dependent Nuclear Localization and Genomic Function Mol. Endocrinol., January 1, 2004; 18(1): 86 - 96. [Abstract] [Full Text] [PDF]
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D.-b. Chen, I. M. Bird, J. Zheng, and R. R. Magness Membrane Estrogen Receptor-Dependent Extracellular Signal-Regulated Kinase Pathway Mediates Acute Activation of Endothelial Nitric Oxide Synthase by Estrogen in Uterine Artery Endothelial Cells Endocrinology, January 1, 2004; 145(1): 113 - 125. [Abstract] [Full Text] [PDF]
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J. Qiu, M. A. Bosch, S. C. Tobias, D. K. Grandy, T. S. Scanlan, O. K. Ronnekleiv, and M. J. Kelly Rapid Signaling of Estrogen in Hypothalamic Neurons Involves a Novel G-Protein-Coupled Estrogen Receptor that Activates Protein Kinase C J. Neurosci., October 22, 2003; 23(29): 9529 - 9540. [Abstract] [Full Text] [PDF]
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O. A. Sukocheva, L. Wang, N. Albanese, S. M. Pitson, M. A. Vadas, and P. Xia Sphingosine Kinase Transmits Estrogen Signaling in Human Breast Cancer Cells Mol. Endocrinol., October 1, 2003; 17(10): 2002 - 2012. [Abstract] [Full Text] [PDF]
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S. Incerpi, S. D'Arezzo, M. Marino, R. Musanti, V. Pallottini, A. Pascolini, and A. Trentalance Short-Term Activation by Low 17{beta}-Estradiol Concentrations of the Na+/H+ Exchanger in Rat Aortic Smooth Muscle Cells: Physiopathological Implications Endocrinology, October 1, 2003; 144(10): 4315 - 4324. [Abstract] [Full Text] [PDF]
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 J. Matthews and J.-A. Gustafsson Estrogen Signaling: A Subtle Balance Between ER{alpha} and ER{beta} Mol. Interv., August 1, 2003; 3(5): 281 - 292. [Abstract] [Full Text] [PDF]
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 J. M. Soares Jr., M. I. Masana, C. Ersahin, and M. L. Dubocovich Functional Melatonin Receptors in Rat Ovaries at Various Stages of the Estrous Cycle J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 694 - 702. [Abstract] [Full Text] [PDF]
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S. Fiorini, M. E. Ferretti, C. Biondi, B. Pavan, L. Lunghi, G. Paganetto, and L. Abelli 17{beta}-Estradiol Stimulates Arachidonate Release from Human Amnion-Like WISH Cells through a Rapid Mechanism Involving a Membrane Receptor Endocrinology, August 1, 2003; 144(8): 3359 - 3367. [Abstract] [Full Text] [PDF]
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L. L. DonCarlos, D. Garcia-Ovejero, S. Sarkey, L. M. Garcia-Segura, and I. Azcoitia Androgen Receptor Immunoreactivity in Forebrain Axons and Dendrites in the Rat Endocrinology, August 1, 2003; 144(8): 3632 - 3638. [Abstract] [Full Text] [PDF]
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