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Science 12 July 1991:
Vol. 253. no. 5016, pp. 197 - 199
DOI: 10.1126/science.1677216
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Articles

Science, Vol 253, Issue 5016, 197-199
Copyright © 1991 by American Association for the Advancement of Science

articles

Function of the homeodomain protein GHF1 in pituitary cell proliferation

JL Castrillo, LE Theill, and M Karin

Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.

Mutations that cause pituitary dwarfism in the mouse reside in the gene encoding the transcription factor growth hormone factor 1 (GHF1 or pit1). These dwarf mice (dw and dwJ) are deficient in growth hormone (GH) and prolactin (PRL) synthesis and exhibit pituitary hypoplasia, suggesting a stem cell defect. With antisense oligonucleotide technology, a cell culture model of this genetic defect was developed. Specific inhibition of GHF1 synthesis by complementary oligonucleotides led to a marked decrease in GH and PRL expression and to a marked decrease in proliferation of somatotrophic cell lines. These results provide direct evidence that the homeodomain protein GHF1 is required not only for the establishment and maintenance of the differentiated phenotype but for cell proliferation as well.


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Cloning and Characterization of the 5'-Flanking Region of the Human Growth Hormone-releasing Hormone Receptor Gene.
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Characterization of Prophet of Pit-1 Gene Expression in Normal Pituitary and Pituitary Adenomas in Humans.
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The Cytogenesis and Pathogenesis of Pituitary Adenomas.
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Multistep Control of Pituitary Organogenesis.
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Pit-1 and GATA-2 Interact and Functionally Cooperate to Activate the Thyrotropin beta -Subunit Promoter.
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Growth Hormone Expression in Murine Bone Marrow Cells Is Independent of the Pituitary Transcription Factor Pit-1.
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p21CIP1-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene..
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Somatostatin Acts by Inhibiting the Cyclic 3',5'-Adenosine Monophosphate (cAMP)/Protein Kinase A Pathway, cAMP Response Element-Binding Protein (CREB) Phosphorylation, and CREB Transcription Potency.
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AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene.
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Molecular Cloning and Characterization of Human Cardiac Homeobox Gene CSX1.
I. Shiojima, I. Komuro, T. Mizuno, R. Aikawa, H. Akazawa, T. Oka, T. Yamazaki, and Y. Yazaki (1996)
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GHF-1/Pit-1 Functions as a Cell-specific Integrator of Ras Signaling by Targeting the Ras Pathway to a Composite Ets-1/GHF-1 Response Element.
A. P. Bradford, K. E. Conrad, P. H. Tran, M. C. Ostrowski, and A. Gutierrez-Hartmann (1996)
J. Biol. Chem. 271, 24639-24648
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Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo.
E Hermesz, S Mackem, and K. Mahon (1996)
Development 122, 41-52
   Abstract »    PDF »
Anterior pituitary cells defective in the cell-autonomous factor, df, undergo cell lineage specification but not expansion.
P. Gage, M. Roller, T. Saunders, L. Scarlett, and S. Camper (1996)
Development 122, 151-160
   Abstract »    PDF »
In Vivo Mutational Analysis of the DNA Binding Domain of the Tissue-specific Transcription Factor, Pit-1.
J. Liang, S. Moye-Rowley, and R. A. Maurer (1995)
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GHF-1-promoter-targeted immortalization of a somatotropic progenitor cell results in dwarfism in transgenic mice..
D Lew, H Brady, K Klausing, K Yaginuma, L E Theill, C Stauber, M Karin, and P L Mellon (1993)
Genes & Dev. 7, 683-693
   Abstract »    PDF »
Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro.
E. Collarini, R Kuhn, C. Marshall, E. Monuki, G Lemke, and W. Richardson (1992)
Development 116, 193-200
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Transcriptional Activation of Mouse sst2 Somatostatin Receptor Promoter by Transforming Growth Factor-beta . INVOLVEMENT OF Smad4.
E. Puente, N. Saint-Laurent, J. Torrisani, C. Furet, A. V. Schally, N. Vaysse, L. Buscail, and C. Susini (2001)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)