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Laboratoire de Génétique Moléculaire Institut de Recherches Cliniques de Montréal Montréal Québec Canada H2W 1R7
The Ptx1 (pituitary homeobox 1) homeobox
transcription factor was isolated as a transcription factor of the
pituitary POMC gene. In corticotrope cells that express POMC,
cell-specific transcription is conferred in part by the synergistic
action of Ptx1 with the basic helix-loop-helix factor NeuroD1. Since
Ptx1 expression precedes pituitary development and differentiation, we
investigated its expression and function in other pituitary lineages.
Ptx1 is expressed in most pituitary-derived cell lines and as is the
related Ptx2 (Rieger) gene. However, Ptx1 appears to be the only Ptx
protein in corticotropes and the predominant one in gonadotrope cells.
Most pituitary hormone-coding gene promoters are activated by Ptx1.
Thus, Ptx1 appears to be a general regulator of pituitary-specific
transcription. In addition, Ptx1 action is synergized by
cell-restricted transcription factors to confer promoter-specific
expression. Indeed, in the somatolactotrope lineage, synergism between
Ptx1 and Pit1 is observed on the PRL promoter, and strong synergism
between Ptx1 and SF-1 is observed in gonadotrope cells on the ßLH
promoter but not on the 
GSU (glycoprotein hormone -subunit gene)
and ßFSH promoters. Synergism between these two classes of factors is
reminiscent of the interaction between the products of the
Drosophila genes Ftz (fushi tarazu) and Ftz-F1. Antisense
RNA experiments performed in T3–1 cells that express the GSU
gene showed that expression of endogenous GSU is highly dependent on
Ptx1 whereas many other genes are not affected. Interestingly, the only
other gene found to be highly dependent on Ptx1 for expression was the
gene for the Lim3/Lhx3 transcription factor. Thus, these experiments
place Ptx1 upstream of Lim3/Lhx3 in a cascade of regulators that appear
to work in a combinatorial code to direct pituitary-, lineage-, and
promoter-specific transcription.
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M.-H. Quentien, F. Pitoia, G. Gunz, M.-P. Guillet, A. Enjalbert, and I. Pellegrini Regulation of Prolactin, GH, and Pit-1 Gene Expression in Anterior Pituitary by Pitx2: An Approach Using Pitx2 Mutants Endocrinology, August 1, 2002; 143(8): 2839 - 2851. [Abstract] [Full Text] [PDF]
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M. M. Zakaria, K.-H. Jeong, C. Lacza, and U. B. Kaiser Pituitary Homeobox 1 Activates the Rat FSH{beta} (rFSH{beta}) Gene through Both Direct and Indirect Interactions with the rFSH{beta} Gene Promoter Mol. Endocrinol., August 1, 2002; 16(8): 1840 - 1852. [Abstract] [Full Text] [PDF]
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P. Melamed, M. Koh, P. Preklathan, L. Bei, and C. Hew Multiple Mechanisms for Pitx-1 Transactivation of a Luteinizing Hormone beta Subunit Gene J. Biol. Chem., July 12, 2002; 277(29): 26200 - 26207. [Abstract] [Full Text] [PDF]
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S. B. Rosenberg and P. L. Mellon An Otx-Related Homeodomain Protein Binds an LH{beta} Promoter Element Important for Activation During Gonadotrope Maturation Mol. Endocrinol., June 1, 2002; 16(6): 1280 - 1298. [Abstract] [Full Text] [PDF]
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L. E. Olson and M. G. Rosenfeld Perspective: Genetic and Genomic Approaches in Elucidating Mechanisms of Pituitary Development Endocrinology, June 1, 2002; 143(6): 2007 - 2011. [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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N. Kimura, S. Tomizawa, K. N. Arai, R. Y. Osamura, and N. Kimura Characterization of 5'-Flanking Region of Rat Somatostatin Receptor sst2 Gene: Transcriptional Regulatory Elements and Activation by Pitx1 and Estrogen Endocrinology, April 1, 2001; 142(4): 1427 - 1441. [Abstract] [Full Text]
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J. J. Tremblay and R. S. Viger GATA Factors Differentially Activate Multiple Gonadal Promoters through Conserved GATA Regulatory Elements Endocrinology, March 1, 2001; 142(3): 977 - 986. [Abstract] [Full Text] [PDF]
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B. Andersen and M. G. Rosenfeld POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease Endocr. Rev., February 1, 2001; 22(1): 2 - 35. [Abstract] [Full Text]
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H. Pincas, K. Amoyel, R. Counis, and J.-N. Laverrière 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 Mol. Endocrinol., February 1, 2001; 15(2): 319 - 337. [Abstract] [Full Text]
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S. Lopez, M.-L. Island, J. Drouin, M.-T. Bandu, N. Christeff, N. Darracq, R. Barbey, J. Doly, D. Thomas, and S. Navarro Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1 Mol. Cell. Biol., October 15, 2000; 20(20): 7527 - 7540. [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. H. Skelly, M. Korbonits, A. Grossman, G. M. Besser, J. P. Monson, J. F. Geddes, and J. M. Burrin Expression of the Pituitary Transcription Factor Ptx-1, But Not That of the Trans-Activating Factor Prop-1, Is Reduced in Human Corticotroph Adenomas and Is Associated with Decreased {alpha}-Subunit Secretion J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2537 - 2542. [Abstract] [Full Text]
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G. Poulin, M. Lebel, M. Chamberland, F. W. Paradis, and J. Drouin Specific Protein-Protein Interaction between Basic Helix-Loop-Helix Transcription Factors and Homeoproteins of the Pitx Family Mol. Cell. Biol., July 1, 2000; 20(13): 4826 - 4837. [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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E. Nishihara, Y. Nagayama, S. Inoue, H. Hiroi, M. Muramatsu, S. Yamashita, and T. Koji Ontogenetic Changes in the Expression of Estrogen Receptor {alpha} and {beta} in Rat Pituitary Gland Detected by Immunohistochemistry Endocrinology, February 1, 2000; 141(2): 615 - 620. [Abstract] [Full Text] [PDF]
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Heritable Disorders of Pituitary Development J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4362 - 4370. [Abstract] [Full Text]
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D. F. Gordon, W. W. Woodmansee, S. R. Lewis, R. A. James, W. M. Wood, and E. C. Ridgway Cloning of the Mouse Somatostatin Receptor Subtype 5 Gene: Promoter Structure and Function Endocrinology, December 1, 1999; 140(12): 5598 - 5608. [Abstract] [Full Text]
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B. A. Amendt, L. B. Sutherland, and A. F. Russo Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail Mol. Cell. Biol., October 1, 1999; 19(10): 7001 - 7010. [Abstract] [Full Text] [PDF]
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R. A. Abbud, R. K. Ameduri, J. S. Rao, T. M. Nett, and J. H. Nilson Chronic Hypersecretion of Luteinizing Hormone in Transgenic Mice Selectively Alters Responsiveness of the {alpha}-Subunit Gene to Gonadotropin-Releasing Hormone and Estrogens Mol. Endocrinol., September 1, 1999; 13(9): 1449 - 1459. [Abstract] [Full Text]
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J. J. Tremblay and R. S. Viger Transcription Factor GATA-4 Enhances Mullerian Inhibiting Substance Gene Transcription through a Direct Interaction with the Nuclear Receptor SF-1 Mol. Endocrinol., August 1, 1999; 13(8): 1388 - 1401. [Abstract] [Full Text]
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 E. R. Norwitz, K.-H. Jeong, and W. W. Chin Molecular Mechanisms of Gonadotropin-Releasing Hormone Receptor Gene Regulation Reproductive Sciences, July 1, 1999; 6(4): 169 - 178. [Abstract] [PDF]
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I. Pellegrini-Bouiller, C. Manrique, G. Gunz, M. Grino, A. J. Zamora, D. Figarella-Branger, F. Grisoli, P. Jaquet, and A. Enjalbert Expression of the Members of the Ptx Family of Transcription Factors in Human Pituitary Adenomas J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2212 - 2220. [Abstract] [Full Text]
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C. Dorn, Q. Ou, J. Svaren, P. A. Crawford, and Y. Sadovsky Activation of Luteinizing Hormone beta Gene by Gonadotropin-releasing Hormone Requires the Synergy of Early Growth Response-1 and Steroidogenic Factor-1 J. Biol. Chem., May 14, 1999; 274(20): 13870 - 13876. [Abstract] [Full Text] [PDF]
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P. L. M. Dahia and A. B. Grossman The Molecular Pathogenesis of Corticotroph Tumors Endocr. Rev., April 1, 1999; 20(2): 136 - 155. [Abstract] [Full Text]
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J. J. Tremblay and J. Drouin Egr-1 Is a Downstream Effector of GnRH and Synergizes by Direct Interaction with Ptx1 and SF-1 To Enhance Luteinizing Hormone beta Gene Transcription Mol. Cell. Biol., April 1, 1999; 19(4): 2567 - 2576. [Abstract] [Full Text] [PDF]
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J.-J. Lareyre, T. Z. Thomas, W.-L. Zheng, S. Kasper, D. E. Ong, M.-C. Orgebin-Crist, and R. J. Matusik A 5-Kilobase Pair Promoter Fragment of the Murine Epididymal Retinoic Acid-binding Protein Gene Drives the Tissue-specific, Cell-specific, and Androgen-regulated Expression of a Foreign Gene in the Epididymis of Transgenic Mice J. Biol. Chem., March 19, 1999; 274(12): 8282 - 8290. [Abstract] [Full Text] [PDF]
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C. Lanctôt, Y. Gauthier, and J. Drouin Pituitary Homeobox 1 (Ptx1) Is Differentially Expressed during Pituitary Development Endocrinology, March 1, 1999; 140(3): 1416 - 1422. [Abstract] [Full Text]
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E. J. Lee, L. M. Anderson, B. Thimmapaya, and J. L. Jameson Targeted Expression of Toxic Genes Directed by Pituitary Hormone Promoters: A Potential Strategy for Adenovirus-Mediated Gene Therapy of Pituitary Tumors J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 786 - 794. [Abstract] [Full Text]
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P. Gage, H Suh, and S. Camper Dosage requirement of Pitx2 for development of multiple organs Development, January 10, 1999; 126(20): 4643 - 4651. [Abstract] [PDF]
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C Lanctot, A Moreau, M Chamberland, M. Tremblay, and J Drouin Hindlimb patterning and mandible development require the Ptx1 gene Development, January 5, 1999; 126(9): 1805 - 1810. [Abstract] [PDF]
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H. Kaji, S. Tai, Y. Okimura, G. Iguchi, Y. Takahashi, H. Abe, and K. Chihara Cloning and Characterization of the 5'-Flanking Region of the Human Growth Hormone Secretagogue Receptor Gene J. Biol. Chem., December 18, 1998; 273(51): 33885 - 33888. [Abstract] [Full Text] [PDF]
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S. L. Asa and S. Ezzat The Cytogenesis and Pathogenesis of Pituitary Adenomas Endocr. Rev., December 1, 1998; 19(6): 798 - 827. [Abstract] [Full Text]
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A Duggan, C Ma, and M Chalfie Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes Development, January 10, 1998; 125(20): 4107 - 4119. [Abstract] [PDF]
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