This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chaudhary, J. Articles by Skinner, M. K. Search for Related Content PubMed PubMed Citation Articles by Chaudhary, J. Articles by Skinner, M. K.

Role of Winged Helix Transcription Factor (WIN) in the Regulation of Sertoli Cell Differentiated Functions: WIN Acts as an Early Event Gene for Follicle-Stimulating Hormone

Center for Reproductive Biology, Washington State University School of Molecular Biosciences, Pullman, Washington 99164-4231

Address all correspondence and requests for reprints to: Dr. Michael K. Skinner, Center for Reproductive Biology, Washington State University School of Molecular Biosciences, Pullman, Washington 99164-4231. E-mail: skinner{at}mail.wsu.edu

Members of the winged helix transcription factor family are known to regulate epithelial cell differentiation by regulating cell-specific gene expression. rWIN is a newly discovered member of the winged helix family shown to be present in the adult rat testis. In the testis the human homolog of rWIN, HFH-11, was localized to the germ cells (i.e. spermatocytes and spermatids) undergoing spermatogenesis. In the present study we show that rWIN is also expressed in testicular Sertoli cells. Sertoli cells are the epithelial component of the seminiferous tubule and provide both the cytoarchitectural support and the microenvironment for developing germ cells. The presence of rWIN in Sertoli cells was confirmed by Northern blot and RT-PCR analysis. The rWIN transcript size in the Sertoli cells was different from the germ cell transcript that is probably due to alternative splicing or modifications of the 3'-untranslated region. At least two spliced variants of rWIN were observed in the Sertoli cells corresponding to the deletion of an exon in the DNA-binding region. Long term stimulation of cultured Sertoli cells with the gonadotropin FSH down-regulated rWIN expression. In contrast, short-term stimulation (2 h) transiently up-regulated rWIN expression. The FSH-induced transient stimulation of rWIN precedes expression of the transferrin gene that is a marker of Sertoli cell differentiation. FSH-induced transferrin promoter activity was inhibited when cultured Sertoli cells were treated with an antisense oligonucleotide to rWIN. Interestingly, the constitutive overexpression of the DNA-binding domain of rWIN also down-regulated transferrin promoter activity. Analysis of the transferrin promoter with various deletion mutations suggested that rWIN acts at an upstream gene of the transferrin promoter. The results indicate that a transient up-regulation of rWIN in part mediates the ability of FSH to activate the transferrin promoter, which can be inhibited with a rWIN antisense oligonucleotide or constitutive expression of the rWIN DNA-binding domain. The current study demonstrates that rWIN acts as an early event gene for FSH actions on Sertoli cells and that rWIN appears to have a role in the regulation of Sertoli cell differentiated functions.

This article has been cited by other articles:

				J. Chaudhary, I. Sadler-Riggleman, J. M. Ague, and M. K. Skinner The Helix-Loop-Helix Inhibitor of Differentiation (ID) Proteins Induce Post-Mitotic Terminally Differentiated Sertoli Cells to Re-Enter the Cell Cycle and Proliferate Biol Reprod, May 1, 2005; 72(5): 1205 - 1217. [Abstract] [Full Text] [PDF]

				M.-T. Teh, S.-T. Wong, G. W. Neill, L. R. Ghali, M. P. Philpott, and A. G. Quinn FOXM1 Is a Downstream Target of Gli1 in Basal Cell Carcinomas Cancer Res., August 15, 2002; 62(16): 4773 - 4780. [Abstract] [Full Text] [PDF]

				M. K. Dahle, L. M. Gronning, A. Cederberg, H. K. Blomhoff, N. Miura, S. Enerback, K. A. Tasken, and K. Tasken Mechanisms of FOXC2- and FOXD1-mediated Regulation of the RIalpha Subunit of cAMP-dependent Protein Kinase Include Release of Transcriptional Repression and Activation by Protein Kinase Balpha and cAMP J. Biol. Chem., June 14, 2002; 277(25): 22902 - 22908. [Abstract] [Full Text] [PDF]

				J. Chaudhary, J. Johnson, G. Kim, and M. K. Skinner Hormonal Regulation and Differential Actions of the Helix-Loop-Helix Transcriptional Inhibitors of Differentiation (Id1, Id2, Id3, and Id4) in Sertoli Cells Endocrinology, May 1, 2001; 142(5): 1727 - 1736. [Abstract] [Full Text]