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Division of Genetics (L.M.H., W.W.C.) and
Endocrine-Hypertension Division (U.B.K.) Department of Medicine
Brigham and Women’s Hospital and Harvard Medical School Boston,
Massachusetts 02115
Department of Obstetrics and Gynecology
(L.M.H.) Tufts University School of Medicine Boston,
Massachusetts 02111
Expression of the LHß gene has been shown to
be modulated by both the orphan nuclear receptor, steroidogenic
factor-1 (SF-1), and the early growth response protein 1, Egr-1. It is
also well known that LHß mRNA levels are increased after hormonal
activation of the protein kinase C (PKC) signaling system, for example
by GnRH; however, the mechanisms by which the PKC system exerts this
effect has not been fully characterized. By transient transfection of
the GH3 cell line, we demonstrate that
activation of the PKC system with the phorbol ester, phorbol
12-myristate 13-acetate (PMA), increases activity of region -207/+5 of
the rat LHß gene promoter (
2-fold) and markedly augments
SF-1-induced stimulation (95-fold in the presence of both factors
vs. 13-fold for SF-1 alone). Mutation of the two previously
identified Egr-1 sites not only prevents Egr-1 effects on the LHß
gene promoter, but also eliminates the synergistic response to PMA and
SF-1 together, findings that were confirmed in a longer construct
spanning region -797/+5. In the gonadotrope-derived cell line,
T3–1, these mutations eliminate the GnRH responsiveness of the
-207/+5 LHß promoter construct. We next show that PMA treatment
(GH3 and T3–1 cells) or GnRH treatment
(T3–1 cells) induces expression of Egr-1, as detected by Egr-1
interaction with Egr-1 DNA-binding sites in the rat LHß gene promoter
sequence. Furthermore, we demonstrate that PMA increases steady-state
Egr-1 mRNA levels via increased Egr-1 transcription. We conclude that
PMA-induced stimulation of LHß gene expression is achieved, at least
in part, by induction of Egr-1 expression.
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T. Zhang, M. W. Wolfe, and M. S. Roberson An Early Growth Response Protein (Egr) 1 cis-Element Is Required for Gonadotropin-releasing Hormone-induced Mitogen-activated Protein Kinase Phosphatase 2 Gene Expression J. Biol. Chem., November 30, 2001; 276(49): 45604 - 45613. [Abstract] [Full Text] [PDF]
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J. S. Jorgensen and J. H. Nilson AR Suppresses Transcription of the LH{beta} Subunit by Interacting with Steroidogenic Factor-1 Mol. Endocrinol., September 1, 2001; 15(9): 1505 - 1516. [Abstract] [Full Text] [PDF]
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L. L. Heckert Activation of the Rat Follicle-Stimulating Hormone Receptor Promoter by Steroidogenic Factor 1 Is Blocked by Protein Kinase A and Requires Upstream Stimulatory Factor Binding to a Proximal E Box Element Mol. Endocrinol., May 1, 2001; 15(5): 704 - 715. [Abstract] [Full Text]
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C. C. Quirk, K. L. Lozada, R. A. Keri, and J. H. Nilson A Single Pitx1 Binding Site Is Essential for Activity of the LH{beta} Promoter in Transgenic Mice Mol. Endocrinol., May 1, 2001; 15(5): 734 - 746. [Abstract] [Full Text]
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G. V. Childs Editorial: Green Fluorescent Proteins Light the Way to a Better Understanding of the Function and Regulation of Specific Anterior Pituitary Cells Endocrinology, December 1, 2000; 141(12): 4331 - 4333. [Full Text] [PDF]
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M. Higa, H. Kanda, T. Kitahashi, M. Ito, T. Shiba, and H. Ando Quantitative Analysis of fushi tarazu Factor 1 Homolog Messenger Ribonucleic Acids in the Pituitary of Salmon at Different Prespawning Stages Biol Reprod, December 1, 2000; 63(6): 1756 - 1763. [Abstract] [Full Text]
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U. B. Kaiser, L. M. Halvorson, and M. T. Chen Sp1, Steroidogenic Factor 1 (SF-1), and Early Growth Response Protein 1 (Egr-1) Binding Sites Form a Tripartite Gonadotropin-Releasing Hormone Response Element in the Rat Luteinizing Hormone-{beta} Gene Promoter: an Integral Role for SF-1 Mol. Endocrinol., August 1, 2000; 14(8): 1235 - 1245. [Abstract] [Full Text]
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R. A. Keri, D. J. Bachmann, A. Behrooz, B. D. Herr, R. K. Ameduri, C. C. Quirk, and J. H. Nilson An NF-Y Binding Site Is Important for Basal, but Not Gonadotropin-releasing Hormone-stimulated, Expression of the Luteinizing Hormone beta Subunit Gene J. Biol. Chem., April 21, 2000; 275(17): 13082 - 13088. [Abstract] [Full Text] [PDF]
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J. Weck, A. C. Anderson, S. Jenkins, P. C. Fallest, and M. A. Shupnik Divergent and Composite Gonadotropin-Releasing Hormone-Responsive Elements in the Rat Luteinizing Hormone Subunit Genes Mol. Endocrinol., April 1, 2000; 14(4): 472 - 485. [Abstract] [Full Text]
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E. Barnea and Y. Bergman Synergy of SF1 and RAR in Activation of Oct-3/4 Promoter J. Biol. Chem., February 25, 2000; 275(9): 6608 - 6619. [Abstract] [Full Text] [PDF]
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M. W. Wolfe The Equine Luteinizing Hormone {beta}-Subunit Promoter Contains Two Functional Steroidogenic Factor-1 Response Elements Mol. Endocrinol., September 1, 1999; 13(9): 1497 - 1510. [Abstract] [Full Text]
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G. B. Call and M. W. Wolfe Gonadotropin-Releasing Hormone Activates the Equine Luteinizing Hormone {beta} Promoter Through a Protein Kinase C/Mitogen-Activated Protein Kinase Pathway Biol Reprod, September 1, 1999; 61(3): 715 - 723. [Abstract] [Full Text]
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M. W. Wolfe and G. B. Call Early Growth Response Protein 1 Binds to the Luteinizing Hormone-{beta} Promoter and Mediates Gonadotropin-Releasing Hormone-Stimulated Gene Expression Mol. Endocrinol., May 1, 1999; 13(5): 752 - 763. [Abstract] [Full Text]
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