| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
(ER)- and ERß-Expressing GT1–7 GnRH Neurons1
Institute for Medical Sciences (D.R., D.D.B.) and the Department of Physiology (D.D.B.), University of Toronto, and Division of Reproductive Science, Toronto Hospital Research Institute, Toronto, Ontario, Canada M5G 2C4
Address all correspondence and requests for reprints to: Denise D. Belsham, Ph.D., Department of Physiology/Division of Reproductive Science, University of Toronto/Toronto Hospital Research Institute, 200 Elizabeth Street, CCRW 3–832, Toronto, Ontario, Canada M5G 2C4. E-mail: d.belsham{at}utoronto.ca
Estrogen has wide-ranging and complex effects on the reproductive axis,
which are often difficult to interpret from in vivo
studies. Estrogen negatively regulates tonic GnRH synthesis and also
plays a pivotal role in the positive regulation of GnRH necessary for
the preovulatory surge. To dissect the mechanisms by which these
divergent effects occur, we attempted to observe the direct action of
estrogen on the regulation of GnRH messenger RNA (mRNA) levels using
the well characterized, GnRH-secreting, hypothalamic cell line, GT1–7.
Using RT-PCR, we first investigated estrogen receptor transcript
expression in GT1–7 neurons. We found that the GT1–7 cells express
both estrogen receptor-
(ER) and the recently described ERß
mRNAs. We also detected the presence of both receptor subtypes in the
GT1–7 neurons by Western blot analysis using specific ER antibodies.
By Northern blot analysis of total GT1–7 RNA, we found that
17ß-estradiol (1 nM) down-regulates GnRH mRNA levels to
approximately 55% of basal levels over a 48-h time course. This effect
appears to occur specifically through an ER-mediated mechanism, as ICI
182,780, a complete ER antagonist, blocks the repression of GnRH mRNA
levels by estradiol. The recently reported ER-specific
agonist/ERß-specific antagonist
2,2-bis-(p-hydroxyphenyl-1,1,1-trichloroethane (HPTE), a
methoxychlor metabolite, also down-regulated GnRH gene expression. The
repression of GnRH mRNA levels appears to occur at the transcriptional
level, as simian virus 40 T antigen mRNA expression, which is under the
control of 2.3 kb of the rat GnRH 5'-regulatory region, mimics the
down-regulation of GnRH after treatment with estradiol. As the rat GnRH
regulatory region in GT1–7 neurons does not appear to harbor a classic
estrogen response element, the mechanism involved in the repression of
GnRH has yet to be determined. These results suggest that estradiol
directly regulates GnRH gene expression at the level of the GnRH neuron
and may exert its neuroendocrine control through direct interaction
with specific receptors expressed in these cells.
This article has been cited by other articles:
 |
|
 |
|
  W. E. Ottowitz, D. D. Dougherty, A. J. Fischman, and J. E. Hall [18F]2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Demonstration of Estrogen Negative and Positive Feedback on Luteinizing Hormone Secretion in Women J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3208 - 3214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pielecka-Fortuna, Z. Chu, and S. M. Moenter Kisspeptin Acts Directly and Indirectly to Increase Gonadotropin-Releasing Hormone Neuron Activity and Its Effects Are Modulated by Estradiol Endocrinology, April 1, 2008; 149(4): 1979 - 1986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Abe, K. L. Keen, and E. Terasawa Rapid Action of Estrogens on Intracellular Calcium Oscillations in Primate Luteinizing Hormone-Releasing Hormone-1 Neurons Endocrinology, March 1, 2008; 149(3): 1155 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nishimura, K. Ui-Tei, K. Saigo, H. Ishii, Y. Sakuma, and M. Kato 17{beta}-Estradiol at Physiological Concentrations Augments Ca2+-Activated K+ Currents via Estrogen Receptor {beta} in the Gonadotropin-Releasing Hormone Neuronal Cell Line GT1-7 Endocrinology, February 1, 2008; 149(2): 774 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morales, M. Gonzalez, R. Marin, M. Diaz, and R. Alonso Estrogen inhibition of norepinephrine responsiveness is initiated at the plasma membrane of GnRH-producing GT1-7 cells J. Endocrinol., July 1, 2007; 194(1): 193 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lindzey, F. L Jayes, M. M Yates, J. F Couse, and K. S Korach The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-{alpha}. J. Endocrinol., October 1, 2006; 191(1): 309 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Titolo, F. Cai, and D. D. Belsham Coordinate Regulation of Neuropeptide Y and Agouti-Related Peptide Gene Expression by Estrogen Depends on the Ratio of Estrogen Receptor (ER) {alpha} to ER{beta} in Clonal Hypothalamic Neurons Mol. Endocrinol., September 1, 2006; 20(9): 2080 - 2092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Cabilla, M. d. C. Diaz, L. I. Machiavelli, A. H. Poliandri, F. A. Quinteros, M. Lasaga, and B. H. Duvilanski 17{beta}-Estradiol Modifies Nitric Oxide-Sensitive Guanylyl Cyclase Expression and Down-Regulates Its Activity in Rat Anterior Pituitary Gland Endocrinology, September 1, 2006; 147(9): 4311 - 4318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Pak, W. C. J. Chung, J. L. Roberts, and R. J. Handa Ligand-Independent Effects of Estrogen Receptor {beta} on Mouse Gonadotropin-Releasing Hormone Promoter Activity Endocrinology, April 1, 2006; 147(4): 1924 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Abe and E. Terasawa Firing Pattern and Rapid Modulation of Activity by Estrogen in Primate Luteinizing Hormone Releasing Hormone-1 Neurons Endocrinology, October 1, 2005; 146(10): 4312 - 4320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, A. Bae, R. S. Swerdloff, A. Iranmanesh, and C. Wang Experimentally Induced Androgen Depletion Accentuates Ethnicity-Related Contrasts in Luteinizing Hormone Secretion in Asian and Caucasian Men J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1632 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van de Stolpe, A. J. Slycke, M. O. Reinders, A. W. M. Zomer, S. Goodenough, C. Behl, A. F. Seasholtz, and P. T. van der Saag Estrogen Receptor (ER)-Mediated Transcriptional Regulation of the Human Corticotropin-Releasing Hormone-Binding Protein Promoter: Differential Effects of ER{alpha} and ER{beta} Mol. Endocrinol., December 1, 2004; 18(12): 2908 - 2923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Selva, O. M. Tirado, N. Toran, C. A. Suarez-Quian, J. Reventos, and F. Munell Estrogen Receptor {beta} Expression and Apoptosis of Spermatocytes of Mice Overexpressing a Rat Androgen-Binding Protein Transgene Biol Reprod, November 1, 2004; 71(5): 1461 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jorgensen, C. C. Quirk, and J. H. Nilson Multiple and Overlapping Combinatorial Codes Orchestrate Hormonal Responsiveness and Dictate Cell-Specific Expression of the Genes Encoding Luteinizing Hormone Endocr. Rev., August 1, 2004; 25(4): 521 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. MATAGNE, M.-C. LEBRETHON, A. GERARD, and J.-P. BOURGUIGNON In Vitro Paradigms for the Study of GnRH Neuron Function and Estrogen Effects Ann. N.Y. Acad. Sci., December 1, 2003; 1007(1): 129 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Navarro, S. A. Saeed, C. Murdock, A. J. Martinez-Fuentes, K. K. Arora, L. Z. Krsmanovic, and K. J. Catt Erratum Mol. Endocrinol., December 1, 2003; 17(12): A - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Petersen, E. N. Ottem, and C. D. Carpenter Direct and Indirect Regulation of Gonadotropin-Releasing Hormone Neurons by Estradiol Biol Reprod, December 1, 2003; 69(6): 1771 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Navarro, S. Abdul Saeed, C. Murdock, A. J. Martinez-Fuentes, K. K. Arora, L. Z. Krsmanovic, and K. J. Catt Regulation of Cyclic Adenosine 3',5'-Monophosphate Signaling and Pulsatile Neurosecretion by Gi-coupled Plasma Membrane Estrogen Receptors in Immortalized Gonadotropin-Releasing Hormone Neurons Mol. Endocrinol., September 1, 2003; 17(9): 1792 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Thanky, R. Slater, and A. E. Herbison Sex Differences in Estrogen-Dependent Transcription of Gonadotropin-Releasing Hormone (GnRH) Gene Revealed in GnRH Transgenic Mice Endocrinology, August 1, 2003; 144(8): 3351 - 3358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Ramos, J. Varayoud, L. Kass, H. Rodriguez, L. Costabel, M. Munoz-de-Toro, and E. H. Luque Bisphenol A Induces Both Transient and Permanent Histofunctional Alterations of the Hypothalamic-Pituitary-Gonadal Axis in Prenatally Exposed Male Rats Endocrinology, July 1, 2003; 144(7): 3206 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Khosravi and P. C. K. Leung Differential Regulation of Gonadotropin-Releasing Hormone (GnRH)I and GnRHII Messenger Ribonucleic Acid by Gonadal Steroids in Human Granulosa Luteal Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 663 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vazquez-Martinez, G. M. Leclerc, M. E. Wierman, and F. R. Boockfor Episodic Activation of the Rat GnRH Promoter: Role of the Homeoprotein Oct-1 Mol. Endocrinol., September 1, 2002; 16(9): 2093 - 2100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sharifi, A. E. Reuss, and S. Wray Prenatal LHRH Neurons in Nasal Explant Cultures Express Estrogen Receptor {beta} Transcript Endocrinology, July 1, 2002; 143(7): 2503 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lyou, E. Hirano, K. Tujioka, Y. Mawatari, K. Hayase, S. Okuyama, and H. Yokogoshi Dietary Genistein Affects Brain Protein Synthesis Rates in Ovariectomized Female Rats J. Nutr., July 1, 2002; 132(7): 2055 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gill, J. L. Sharpless, K. Rado, and J. E. Hall Evidence That GnRH Decreases with Gonadal Steroid Feedback but Increases with Age in Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2290 - 2296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Potier, M. Karl, F. Zheng, S. J. Elliot, G. E. Striker, and L. J. Striker Estrogen-Related Abnormalities in Glomerulosclerosis-Prone Mice : Reduced Mesangial Cell Estrogen Receptor Expression and Prosclerotic Response to Estrogens Am. J. Pathol., May 1, 2002; 160(5): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Waters, S. Safe, and K. W. Gaido Differential Gene Expression in Response to Methoxychlor and Estradiol through ER{alpha}, ER{beta}, and AR in Reproductive Tissues of Female Mice Toxicol. Sci., September 1, 2001; 63(1): 47 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Pak, G. R. Lynch, and P.-S. Tsai Testosterone and Estrogen Act via Different Pathways to Inhibit Puberty in the Male Siberian Hamster (Phodopus sungorus) Endocrinology, August 1, 2001; 142(8): 3309 - 3316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. POTIER, S. J. ELLIOT, I. TACK, O. LENZ, G. E. STRIKER, L. J. STRIKER, and M. KARL Expression and Regulation of Estrogen Receptors in Mesangial Cells: Influence on Matrix Metalloproteinase-9 J. Am. Soc. Nephrol., February 1, 2001; 12(2): 241 - 251. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. S. Krumenacker, S. M. Hyder, and F. Murad Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus PNAS, January 16, 2001; 98(2): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayase, M. Tanaka, K. Tujioka, E. Hirano, O. Habuchi, and H. Yokogoshi 17-{beta}-Estradiol Affects Brain Protein Synthesis Rate in Ovariectomized Female Rats J. Nutr., January 1, 2001; 131(1): 123 - 126. [Abstract] [Full Text]
|
|
|
|
|
|
F. J. Hayes, S. B. Seminara, S. DeCruz, P. A. Boepple, and W. F. Crowley Jr. Aromatase Inhibition in the Human Male Reveals a Hypothalamic Site of Estrogen Feedback J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3027 - 3035. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
