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Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Rotterdam; and Hubrecht Laboratory, Netherlands Institute for Developmental Biology (J.P.d.W.), Utrecht, The Netherlands
Address all correspondence and requests for reprints to: Dr. J. W. M. Martens, Department of Endocrinology and Reproduction, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: martens{at}endov.fgg.eur.nl
To gain more insight in the mechanism of action of inhibin, we studied the effect of inhibin on activin signaling in Chinese hamster ovary cells. Inhibin specifically counteracted activin-induced expression of a plasminogen activator inhibitor 1 promoter element (3TP) and of the junB gene, but was ineffective when the responses were induced by transforming growth factor-ß. This indicates that inhibin acts only on the activin-specific part of these signaling cascades. Using a constitutively active activin type IB receptor we determined whether inhibin acted at the level of the activin-receptor complex or downstream of it. The mutant activin receptor stimulated the expression of the 3TP promoter in the absence of activin. This stimulation was insensitive to inhibin, indicating that inhibin acts exclusively at or upstream of this activin type I receptor. In addition, competition studies using labeled activin showed that inhibin displaced activin from the activin type II receptors, especially from the activin type IIB receptor, but not from the type I receptors. In conclusion, these data show that in Chinese hamster ovary cells inhibin acts directly at the activin receptor complex, most likely through displacement of activin from the activin type II receptor.
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L. A. MacConell, A. M. O. Leal, and W. W. Vale The Distribution of Betaglycan Protein and mRNA in Rat Brain, Pituitary, and Gonads: Implications for a Role for Betaglycan in Inhibin-Mediated Reproductive Functions Endocrinology, March 1, 2002; 143(3): 1066 - 1075. [Abstract] [Full Text] [PDF]
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S. C. Chapman and T. K. Woodruff Modulation of Activin Signal Transduction by Inhibin B and Inhibin-Binding Protein (InhBP) Mol. Endocrinol., April 1, 2001; 15(4): 668 - 679. [Abstract] [Full Text]
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C. A. Harrison, P. G. Farnworth, K. L. Chan, P. G. Stanton, G. T. Ooi, J. K. Findlay, and D. M. Robertson Identification of Specific Inhibin A-Binding Proteins on Mouse Leydig (TM3) and Sertoli (TM4) Cell Lines Endocrinology, April 1, 2001; 142(4): 1393 - 1402. [Abstract] [Full Text]
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T. M. Pierson, Y. Wang, F. J. DeMayo, M. M. Matzuk, S. Y. Tsai, and B. W. O’Malley Regulable Expression of Inhibin A in Wild-Type and Inhibin {alpha} Null Mice Mol. Endocrinol., July 1, 2000; 14(7): 1075 - 1085. [Abstract] [Full Text]
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M. M. Matzuk Editorial: In Search of Binding--Identification of Inhibin Receptors Endocrinology, July 1, 2000; 141(7): 2281 - 2284. [Full Text] [PDF]
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H. Chong, S. A. Pangas, D. J. Bernard, E. Wang, J. Gitch, W. Chen, L. B. Draper, E. T. Cox, and T. K. Woodruff Structure and Expression of a Membrane Component of the Inhibin Receptor System Endocrinology, July 1, 2000; 141(7): 2600 - 2607. [Abstract] [Full Text] [PDF]
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S. C. Riley, R. Leask, C. Balfour, J. E. Brennand, and N. P. Groome Production of inhibin forms by the fetal membranes, decidua, placenta and fetus at parturition Hum. Reprod., March 1, 2000; 15(3): 578 - 583. [Abstract] [Full Text] [PDF]
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Y. Pang and W. Ge Activin Stimulation of Zebrafish Oocyte Maturation in Vitro and Its Potential Role in Mediating Gonadotropin-Induced Oocyte Maturation Biol Reprod, October 1, 1999; 61(4): 987 - 992. [Abstract] [Full Text]
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A. Delbaere, Y. Sidis, and A. L. Schneyer Differential Response to Exogenous and Endogenous Activin in a Human Ovarian Teratocarcinoma-Derived Cell Line (PA-1): Regulation by Cell Surface Follistatin Endocrinology, June 1, 1999; 140(6): 2463 - 2470. [Abstract] [Full Text]
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A. Lux, L. Attisano, and D. A. Marchuk Assignment of Transforming Growth Factor beta 1 and beta 3 and a Third New Ligand to the Type I Receptor ALK-1 J. Biol. Chem., April 9, 1999; 274(15): 9984 - 9992. [Abstract] [Full Text] [PDF]
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T. K. Woodruff Editorial: Hope, Hypothesis, and the Inhibin Receptor. Does Specific Inhibin Binding Suggest There Is a Specific Inhibin Receptor? Endocrinology, January 1, 1999; 140(1): 3 - 5. [Full Text]
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R. Hertan, P. G. Farnworth, K. L. Fitzsimmons, and D. M. Robertson Identification of High Affinity Binding Sites for Inhibin on Ovine Pituitary Cells in Culture Endocrinology, January 1, 1999; 140(1): 6 - 12. [Abstract] [Full Text]
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Y. Sidis,, T. Fujiwara,, L. Leykin,, K. Isaacson,, T. Toth,, and A. L. Schneyer Characterization of Inhibin/Activin Subunit, Activin Receptor, and Follistatin Messenger Ribonucleic Acid in Human and Mouse Oocytes: Evidence for Activin's Paracrine Signaling from Granulosa Cells to Oocytes Biol Reprod, October 1, 1998; 59(4): 807 - 812. [Abstract] [Full Text]
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