| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 29, 2003
Accepted on November 25, 2003
1 Departments of Anatomy & Cell Biology, and Neurology, and Centers for Neurobiology & Behavior and Reproductive Sciences, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
* To whom correspondence should be addressed. E-mail: cdt2{at}columbia.edu.
Until 1996, when estrogen receptor-
(ER-) was discovered, life seemed simple. The gonadal steroid hormone 17-estradiol had one receptor, the estrogen receptor, a ligand-inducible nuclear transcription factor. Estrogen receptor variants, the result of bp insertions, transitions, and deletions as well as alternative splicing, were considered abnormal and a prominent feature of breast cancer. Since then, like many other scientific beliefs, this concept has increased dramatically in complexity, and we are now faced with an ever-increasing array of estrogen-binding proteins, putative estrogen receptors, in the brain as well as in the extra-neural targets of estrogen. The end is unlikely to be in sight. Some of these putative receptors have been localized to plasma or nuclear membranes; others to the cytoplasm and/or nucleus. The molecular characteristics of membrane estrogen receptors are still in question, and, in most instances, the proteins have not been sequenced or cloned. However, based on transfection and immunohistochemistry, the generally held view, if not dogma, maintains that both nuclear and plasma-membrane-associated ERs probably originate from the same gene and transcript that produce the classical intranuclear receptors, ER-
and ER-. However, the physiological relatedness of this observation remains open to question. This review addresses evidence that, in addition to ER- and ER-, there exist a variety of non-ER-/non-ER- nuclear, cytoplasmic and plasma membrane estrogen receptors in the brain, including G protein-coupled receptors, a novel, developmentally regulated, membrane-associated estrogen receptor "ER-X", a functional, truncated ER- variant ER-46 and a putative estrogen receptor (pER) that is immunochemically, structurally, and functionally completely distinct from ER- and ER-.
•
ER- •
"ER-X" •
G-protein-coupled receptors •
brain •
caveolae •
caveolar-like membranes
This article has been cited by other articles:
 |
|
 |
|
  B. C. Wadas and S. A. Tobet Unique Estrogenic Mechanisms for Unique Gonadotropin-Releasing Hormone Neurons? Endocrinology, November 1, 2008; 149(11): 5325 - 5327. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vagnerova, I. P. Koerner, and P. D. Hurn Gender and the Injured Brain Anesth. Analg., July 1, 2008; 107(1): 201 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Miller and S. P. Duckles Vascular Actions of Estrogens: Functional Implications Pharmacol. Rev., June 1, 2008; 60(2): 210 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D. Ullrich, A. Krust, P. Collins, and K. T. MacLeod Genomic deletion of estrogen receptors ER{alpha} and ER{beta} does not alter estrogen-mediated inhibition of Ca2+ influx and contraction in murine cardiomyocytes Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2421 - H2427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. McCARTHY Estradiol and the Developing Brain Physiol Rev, January 1, 2008; 88(1): 91 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Arreguin-Arevalo, T. L. Davis, and T. M. Nett Differential Modulation of Gonadotropin Secretion by Selective Estrogen Receptor 1 and Estrogen Receptor 2 Agonists in Ovariectomized Ewes Biol Reprod, August 1, 2007; 77(2): 320 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C Garrido-Gracia, A. Gordon, C. Bellido, R. Aguilar, I. Barranco, Y. Millan, J. M. de las Mulas, and J. E Sanchez-Criado The integrated action of oestrogen receptor isoforms and sites with progesterone receptor in the gonadotrope modulates LH secretion: evidence from tamoxifen-treated ovariectomized rats J. Endocrinol., April 1, 2007; 193(1): 107 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Coiret, A.-S. Borowiec, P. Mariot, H. Ouadid-Ahidouch, and F. Matifat The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells Mol. Pharmacol., March 1, 2007; 71(3): 843 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jones, A. Beda, A. M.V. Ward, C. Osmond, D. I.W. Phillips, V. M. Moore, and D. M. Simpson Size at Birth and Autonomic Function During Psychological Stress Hypertension, March 1, 2007; 49(3): 548 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Veliskova Estrogens and Epilepsy: Why Are We So Excited? Neuroscientist, February 1, 2007; 13(1): 77 - 88. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Zhao, K. O'Neill, and R. D. Brinton Estrogenic Agonist Activity of ICI 182,780 (Faslodex) in Hippocampal Neurons: Implications for Basic Science Understanding of Estrogen Signaling and Development of Estrogen Modulators with a Dual Therapeutic Profile J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1124 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Morrison, R. D. Brinton, P. J. Schmidt, and A. C. Gore Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women J. Neurosci., October 11, 2006; 26(41): 10332 - 10348. [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Fraser, E. Beyret, S. R. Milligan, and S. A. Adeoya-Osiguwa Effects of estrogenic xenobiotics on human and mouse spermatozoa Hum. Reprod., May 1, 2006; 21(5): 1184 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Balthazart, M. Baillien, and G. F. Ball Rapid Control of Brain Aromatase Activity by Glutamatergic Inputs Endocrinology, January 1, 2006; 147(1): 359 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Merot, F. Ferriere, E. Debroas, G. Flouriot, D. Duval, and C. Saligaut Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor J. Mol. Endocrinol., October 1, 2005; 35(2): 257 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J Giltay, K. H Kho, B. A Blansjaar, M. M Verbeek, P B. H Geurtz, J. M Geleijnse, and L. J G Gooren The sex difference of plasma homovanillic acid is unaffected by cross-sex hormone administration in transsexual subjects J. Endocrinol., October 1, 2005; 187(1): 109 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chesnoy-Marchais The Estrogen Receptor Modulator Tamoxifen Enhances Spontaneous Glycinergic Synaptic Inhibition of Hypoglossal Motoneurons Endocrinology, October 1, 2005; 146(10): 4302 - 4311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E Sanchez-Criado, C. Bellido, R. Aguilar, and J. C Garrido-Gracia A paradoxical inhibitory effect of oestradiol-17{beta} on GnRH self-priming in pituitaries from tamoxifen-treated rats J. Endocrinol., July 1, 2005; 186(1): 43 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Miller, T. Jover, H. W. Cohen, R. S. Zukin, and A. M. Etgen Estrogen Can Act via Estrogen Receptor {alpha} and {beta} to Protect Hippocampal Neurons against Global Ischemia-Induced Cell Death Endocrinology, July 1, 2005; 146(7): 3070 - 3079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hasbi, B. F. O'Dowd, and S. R. George A G Protein-Coupled Receptor For Estrogen: The End Of The Search? Mol. Interv., June 1, 2005; 5(3): 158 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Vaskivuo, M. Maentausta, S. Torn, O. Oduwole, A. Lonnberg, R. Herva, V. Isomaa, and J. S. Tapanainen Estrogen Receptors and Estrogen-Metabolizing Enzymes in Human Ovaries during Fetal Development J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3752 - 3756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Boulware, J. P. Weick, B. R. Becklund, S. P. Kuo, R. D. Groth, and P. G. Mermelstein Estradiol Activates Group I and II Metabotropic Glutamate Receptor Signaling, Leading to Opposing Influences on cAMP Response Element-Binding Protein J. Neurosci., May 18, 2005; 25(20): 5066 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Benvenuti, P. Luciani, G. B. Vannelli, S. Gelmini, E. Franceschi, M. Serio, and A. Peri Estrogen and Selective Estrogen Receptor Modulators Exert Neuroprotective Effects and Stimulate the Expression of Selective Alzheimer's Disease Indicator-1, a Recently Discovered Antiapoptotic Gene, in Human Neuroblast Long-Term Cell Cultures J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1775 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. D. Blaustein Can You Teach an Old Dogma New Tricks? Endocrinology, March 1, 2004; 145(3): 1055 - 1056. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
