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Children’s Hospital (I.K., M.H.), University of Helsinki, 00290 Helsinki, Finland; the Departments of Pediatrics (M.B., S.B.P.-T., D.B.W., M.H.) and Molecular Biology and Pharmacology (D.B.W.), Washington University, St. Louis, Missouri 63110; the Departments of Physiology (N.R., J.T., I.T.H.) and Pediatrics (J.T.), University of Turku, 20520 Turku, Finland; and the Department of Obstetrics and Gynecology, University of Oulu (J.S.T.), 90220 Oulu, Finland
Address all correspondence and requests for reprints to: Dr. Markku Heikinheimo, M.D., Ph.D., Children’s Hospital, University of Helsinki, Stenbäckinkatu 11, 00290 Helsinki, Finland. E-mail: markku.heikinheimo{at}helsinki.fi
Previous studies have shown that transcription factors GATA-4 and
GATA-6 are expressed in granulosa and thecal cells of the mouse ovary
and that GATA-4 expression in ovarian tissue is regulated by
gonadotropins. Given the emerging role of GATA-4 and GATA-6 in gonadal
cells, we have now studied the expression and regulation of these
factors in the mouse testis and testicular cell lines. In
situ hybridization demonstrated GATA-4 messenger RNA (mRNA) in
the fetal testis at 13.5 days postcoitum. Both GATA-4 and GATA-6
transcripts were observed in late fetal, neonatal, juvenile, and adult
Sertoli cells. In addition, GATA-4 mRNA was detected in interstitial
cells throughout development. Immunohistochemistry demonstrated GATA-4
protein in both Sertoli and Leydig cells in postnatal animals. The
regulation of GATA-4 and GATA-6 expression was explored using
established testicular cell lines. Treatment of Leydig tumor cell lines
with hCG resulted in a modest, but statistically significant, increase
in the steady state level of GATA-4 mRNA, comparable to the previously
described effect of FSH on GATA-4 expression in Sertoli cell lines.
Gonadotropin or androgen action was not, however, a prerequisite for
the basal expression of GATA-4 or GATA-6 in the testis, as their
presence in Sertoli and Leydig cells was demonstrated in genetically
hypogonadal hpg mice, in rats treated with GnRH receptor
antagonist, and in Sertoli cells after chemical abolition of Leydig
cells. Cotransfection studies using a GATA-4 expression plasmid and an
inhibin 
promoter/reporter gene construct in Leydig and granulosa
tumor cell lines revealed that the inhibin promoter harboring
essential GATA-binding sites can be trans-activated by
GATA-4. In light of these results, we propose that transcription
factors GATA-4 and GATA-6 play differing roles in the maturation and
function of testicular somatic cells.
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M. Bielinska, H. Parviainen, S. B. Porter-Tinge, S. Kiiveri, E. Genova, N. Rahman, I. T. Huhtaniemi, L. J. Muglia, M. Heikinheimo, and D. B. Wilson Mouse Strain Susceptibility to Gonadectomy-Induced Adrenocortical Tumor Formation Correlates with the Expression of GATA-4 and Luteinizing Hormone Receptor Endocrinology, September 1, 2003; 144(9): 4123 - 4133. [Abstract] [Full Text] [PDF]
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J. J. Tremblay and R. S. Viger Transcription Factor GATA-4 Is Activated by Phosphorylation of Serine 261 via the cAMP/Protein Kinase A Signaling Pathway in Gonadal Cells J. Biol. Chem., June 6, 2003; 278(24): 22128 - 22135. [Abstract] [Full Text] [PDF]
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 I. Ketola, J. Toppari, T. Vaskivuo, R. Herva, J. S. Tapanainen, and M. Heikinheimo Transcription Factor GATA-6, Cell Proliferation, Apoptosis, and Apoptosis-Related Proteins Bcl-2 and Bax in Human Fetal Testis J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1858 - 1865. [Abstract] [Full Text] [PDF]
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M. Anttonen, I. Ketola, H. Parviainen, A.-K. Pusa, and M. Heikinheimo FOG-2 and GATA-4 Are Coexpressed in the Mouse Ovary and Can Modulate Mullerian-Inhibiting Substance Expression Biol Reprod, April 1, 2003; 68(4): 1333 - 1340. [Abstract] [Full Text] [PDF]
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M. K. Rao, C. M. Wayne, M. L. Meistrich, and M. F. Wilkinson Pem Homeobox Gene Promoter Sequences that Direct Transcription in a Sertoli Cell-Specific, Stage-Specific, and Androgen-Dependent Manner in the Testis in Vivo Mol. Endocrinol., February 1, 2003; 17(2): 223 - 233. [Abstract] [Full Text] [PDF]
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C. Gillio-Meina, Y. Y. Hui, and H. A. LaVoie GATA-4 and GATA-6 Transcription Factors: Expression, Immunohistochemical Localization, and Possible Function in the Porcine Ovary Biol Reprod, February 1, 2003; 68(2): 412 - 422. [Abstract] [Full Text] [PDF]
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C. M. Wayne, K. Sutton, and M. F. Wilkinson Expression of the Pem Homeobox Gene in Sertoli Cells Increases the Frequency of Adjacent Germ Cells with Deoxyribonucleic Acid Strand Breaks Endocrinology, December 1, 2002; 143(12): 4875 - 4885. [Abstract] [Full Text] [PDF]
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J. J. Tremblay, F. Hamel, and R. S. Viger Protein Kinase A-Dependent Cooperation between GATA and CCAAT/Enhancer-Binding Protein Transcription Factors Regulates Steroidogenic Acute Regulatory Protein Promoter Activity Endocrinology, October 1, 2002; 143(10): 3935 - 3945. [Abstract] [Full Text] [PDF]
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N. M. Robert, J. J. Tremblay, and R. S. Viger Friend of GATA (FOG)-1 and FOG-2 Differentially Repress the GATA-Dependent Activity of Multiple Gonadal Promoters Endocrinology, October 1, 2002; 143(10): 3963 - 3973. [Abstract] [Full Text] [PDF]
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S. Kiiveri, J. Liu, M. Westerholm-Ormio, N. Narita, D. B. Wilson, R. Voutilainen, and M. Heikinheimo Differential Expression of GATA-4 and GATA-6 in Fetal and Adult Mouse and Human Adrenal Tissue Endocrinology, August 1, 2002; 143(8): 3136 - 3143. [Abstract] [Full Text] [PDF]
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S. Basciani, S. Mariani, M. Arizzi, S. Ulisse, N. Rucci, E. A. Jannini, C. D. Rocca, A. Manicone, C. Carani, G. Spera, et al. Expression of Platelet-Derived Growth Factor-A (PDGF-A), PDGF-B, and PDGF Receptor-{alpha} and -{beta} during Human Testicular Development and Disease J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2310 - 2319. [Abstract] [Full Text] [PDF]
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Z. Zhang, A. Z. Wu, Z.-M. Feng, D. Mruk, C. Y. Cheng, and C.-L. C. Chen Gonadotropins, via cAMP, Negatively Regulate GATA-1 Gene Expression in Testicular Cells Endocrinology, March 1, 2002; 143(3): 829 - 836. [Abstract] [Full Text] [PDF]
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T. E. Vaskivuo, M. Anttonen, R. Herva, H. Billig, M. Dorland, E. R. te Velde, F. Stenback, M. Heikinheimo, and J. S. Tapanainen Survival of Human Ovarian Follicles from Fetal to Adult Life: Apoptosis, Apoptosis-Related Proteins, and Transcription Factor GATA-4 J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3421 - 3429. [Abstract] [Full Text] [PDF]
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J. J. Tremblay and R. S. Viger Nuclear Receptor Dax-1 Represses the Transcriptional Cooperation Between GATA-4 and SF-1 in Sertoli Cells Biol Reprod, April 1, 2001; 64(4): 1191 - 1199. [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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Z.-M. Feng, A. Z. Wu, Z. Zhang, and C.-L. C. Chen GATA-1 and GATA-4 Transactivate Inhibin/Activin {beta}-B-Subunit Gene Transcription in Testicular Cells Mol. Endocrinol., November 1, 2000; 14(11): 1820 - 1835. [Abstract] [Full Text]
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I. Ketola, V. Pentikäinen, T. Vaskivuo, V. Ilvesmäki, R. Herva, L. Dunkel, J. S. Tapanainen, J. Toppari, and M. Heikinheimo Expression of Transcription Factor GATA-4 during Human Testicular Development and Disease J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3925 - 3931. [Abstract] [Full Text]
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M. P. E. Laitinen, M. Anttonen, I. Ketola, D. B. Wilson, O. Ritvos, R. Butzow, and M. Heikinheimo Transcription Factors GATA-4 and GATA-6 and a GATA Family Cofactor, FOG-2, Are Expressed in Human Ovary and Sex Cord-Derived Ovarian Tumors J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3476 - 3483. [Abstract] [Full Text]
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C. R. Wooton-Kee and B. J. Clark Steroidogenic Factor-1 Influences Protein-Deoxyribonucleic Acid Interactions within the Cyclic Adenosine 3',5'-Monophosphate-Responsive Regions of the Murine Steroidogenic Acute Regulatory Protein Gene Endocrinology, April 1, 2000; 141(4): 1345 - 1355. [Abstract] [Full Text] [PDF]
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 S. Siltanen, M. Anttonen, P. Heikkila, N. Narita, M. Laitinen, O. Ritvos, D. B. Wilson, and M. Heikinheimo Transcription Factor GATA-4 Is Expressed in Pediatric Yolk Sac Tumors Am. J. Pathol., December 1, 1999; 155(6): 1823 - 1829. [Abstract] [Full Text] [PDF]
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