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Science 30 August 1996:
Vol. 273. no. 5279, pp. 1219 - 1221
DOI: 10.1126/science.273.5279.1219
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Reports

Luteinizing Hormone Deficiency and Female Infertility in Mice Lacking the Transcription Factor NGFI-A (Egr-1)

Stephen L. Lee, Yoel Sadovsky, Alexander H. Swirnoff, Jeffrey A. Polish, Pam Goda, Galina Gavrilina, Jeffrey Milbrandt *

The immediate-early transcription factor NGFI-A (also called Egr-1, zif/268, or Krox-24) is thought to couple extracellular signals to changes in gene expression. Although activins and inhibins regulate follicle-stimulating hormone (FSH) synthesis, no factor has been identified that exclusively regulates luteinizing hormone (LH) synthesis. An analysis of NGFI-A-deficient mice derived from embryonic stem cells demonstrated female infertility that was secondary to LH-beta deficiency. Ovariectomy led to increased amounts of FSH-beta but not LH-beta messenger RNA, which suggested a pituitary defect. A conserved, canonical NGFI-A site in the LH-beta promoter was required for synergistic activation by NGFI-A and steroidogenic factor-1 (SF-1). NGFI-A apparently influences female reproductive capacity through its regulation of LH-beta transcription.

S. L. Lee, A. H. Swirnoff, P. Goda, G. Gavrilina, J. Milbrandt, Departments of Pathology and Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Y. Sadovsky and J. A. Polish, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed.


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Mol. Endocrinol. 16, 1280-1298
   Abstract »    Full Text »    PDF »
Perspective: Genetic and Genomic Approaches in Elucidating Mechanisms of Pituitary Development.
L. E. Olson and M. G. Rosenfeld (2002)
Endocrinology 143, 2007-2011
   Abstract »    Full Text »    PDF »
Early Growth Response Gene-1 Regulates the Expression of the Rat Luteinizing Hormone Receptor Gene.
M. Yoshino, T. Mizutani, K. Yamada, M. Tsuchiya, T. Minegishi, T. Yazawa, H. Kawata, T. Sekiguchi, T. Kajitani, and K. Miyamoto (2002)
Biol Reprod 66, 1813-1819
   Abstract »    Full Text »    PDF »
Pituitary Development: Regulatory Codes in Mammalian Organogenesis.
K. M. Scully and M. G. Rosenfeld (2002)
Science 295, 2231-2235
   Abstract »    Full Text »    PDF »
Sp1 and Egr1 Regulate Transcription of the Dmrt1 Gene in Sertoli Cells.
N. Lei and L. L. Heckert (2002)
Biol Reprod 66, 675-684
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GnRH Regulates Early Growth Response Protein 1 Transcription Through Multiple Promoter Elements.
W. R. Duan, M. Ito, Y. Park, E. T. Maizels, M. Hunzicker-Dunn, and J. L. Jameson (2002)
Mol. Endocrinol. 16, 221-233
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Coating Stents With Antirestenotic Drugs: The Blunderbuss or the Magic Bullet? Response.
H. C. Lowe, L. M. Khachigian, J. Sun, S. O. Marx, H.-J. Chen, A. R. Marks, L. E. Rabbani, and M. Poon (2002)
Circulation 105 , e29
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Experience-Dependent Plasticity of Mouse Visual Cortex in the Absence of the Neuronal Activity-Dependent Marker egr1/zif268.
N. Mataga, S. Fujishima, B. G. Condie, and T. K. Hensch (2001)
J. Neurosci. 21, 9724-9732
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An Early Growth Response Protein (Egr) 1 cis-Element Is Required for Gonadotropin-releasing Hormone-induced Mitogen-activated Protein Kinase Phosphatase 2 Gene Expression.
T. Zhang, M. W. Wolfe, and M. S. Roberson (2001)
J. Biol. Chem. 276, 45604-45613
   Abstract »    Full Text »    PDF »
Upregulation of transcription factors in lung in the early phase of postpneumonectomy lung growth.
L. J. Landesberg, R. Ramalingam, K. Lee, T. K. Rosengart, and R. G. Crystal (2001)
Am J Physiol Lung Cell Mol Physiol 281, L1138-L1149
   Abstract »    Full Text »    PDF »
Metabolism of Vanoxerine, 1-[2-[bis(4-Fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) Piperazine, by Human Cytochrome P450 Enzymes.
S. A. Cherstniakova, D. Bi, D. R. Fuller, J. Z. Mojsiak, J. M. Collins, and L. R. Cantilena (2001)
Drug Metab. Dispos. 29, 1216-1220
   Abstract »    Full Text »    PDF »
Perspective: The Ovarian Follicle--A Perspective in 2001.
J. S. Richards (2001)
Endocrinology 142, 2184-2193
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Cell-Specific Transcriptional Regulation of Follicle-Stimulating Hormone-{beta} by Activin and Gonadotropin-Releasing Hormone in the L{beta}T2 Pituitary Gonadotrope Cell Model.
F. Pernasetti, V. V. Vasilyev, S. B. Rosenberg, J. S. Bailey, H.-J. Huang, W. L. Miller, and P. L. Mellon (2001)
Endocrinology 142, 2284-2295
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A Single Pitx1 Binding Site Is Essential for Activity of the LH{beta} Promoter in Transgenic Mice.
C. C. Quirk, K. L. Lozada, R. A. Keri, and J. H. Nilson (2001)
Mol. Endocrinol. 15, 734-746
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Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility.
L. J. Cushman, D. E. Watkins-Chow, M. L. Brinkmeier, L. T. Raetzman, A. L. Radak, R. V. Lloyd, and S. A. Camper (2001)
Hum. Mol. Genet. 10, 1141-1153
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The Transcription Factor Early Growth-response Factor 1 Modulates Tumor Necrosis Factor-{alpha}, Immunoglobulin E, and Airway Responsiveness in Mice.
E. S. SILVERMAN, G. T. DE SANCTIS, J. BOYCE, J. A. MACLEAN, A. JIAO, F. H. Y. GREEN, H. GRASEMANN, D. FAUNCE, G. FITZMAURICE, G.-P. SHI, et al. (2001)
Am. J. Respir. Crit. Care Med. 163, 778-785
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Unique effects of zinc protoporphyrin on HO-1 induction and apoptosis.
G. Yang, X. Nguyen, J. Ou, P. Rekulapelli, D. K. Stevenson, and P. A. Dennery (2001)
Blood 97, 1306-1313
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Proximal cis-Acting Elements, Including Steroidogenic Factor 1, Mediate the Efficiency of a Distal Enhancer in the Promoter of the Rat Gonadotropin-Releasing Hormone Receptor Gene.
H. Pincas, K. Amoyel, R. Counis, and J.-N. Laverrière (2001)
Mol. Endocrinol. 15, 319-337
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Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function.
L Zhao, M Bakke, Y Krimkevich, L. Cushman, A. Parlow, S. Camper, and K. Parker (2001)
Development 128, 147-154
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Expression and Localization of Luteinizing Hormone Receptor in the Female Mouse Reproductive Tract.
M. Zheng, H. Shi, D. L. Segaloff, and B. J. Van Voorhis (2001)
Biol Reprod 64, 179-187
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