Document Detail

Role of the basic helix-loop-helix protein ITF2 in the hormonal regulation of Sertoli cell differentiation.
MedLine Citation:
PMID:  16425294     Owner:  NLM     Status:  MEDLINE    
Sertoli cells are a post-mitotic terminally differentiated cell population that forms the seminiferous tubules in the adult testis and provides the microenvironment and structural support for developing germ cells. During pubertal development, Sertoli cells are responsive to follicle-stimulating hormone (FSH) to promote the expression of differentiated gene products. The basic helix-loop-helix (bHLH) and inhibitors of differentiation (Id) transcription factors are involved in the differentiation of a variety of cell lineages during development. Both bHLH and Id transcription factors have been identified in Sertoli cells. A yeast two-hybrid screen was conducted using a rat Sertoli cell cDNA library to identify bHLH dimerization partners for the Id1 transcription factor. The ubiquitous bHLH protein ITF2 (i.e., E2-2) was identified as one of the interacting partners. The current study investigates the expression and function of ITF2 in Sertoli cells. ITF2 was found to be ubiquitously expressed in all testicular cell types including germ cells, peritubular myoid cells, and Sertoli cells. Stimulation of cultured Sertoli cells with FSH or dibutryl cAMP resulted in a transient decrease in expression of ITF2 mRNA levels followed by a rise in expression with FSH treatment. ITF2 expression was at its highest in mid-pubertal 20-day-old rat Sertoli cells. ITF2 was found to directly bind to negative acting Id HLH proteins and positive acting bHLH proteins such as scleraxis. Transient overexpression of ITF2 protein in cultured Sertoli cells stimulated transferrin promoter activity, which is a marker of Sertoli cell differentiation. Co-transfections of ITF2 and Id proteins sequestered the inhibitory effects of the Id family of proteins. Observations suggest ITF2 can enhance FSH actions through suppressing the inhibitory actions of the Id family of proteins and increasing the actions of stimulatory bHLH proteins (i.e., scleraxis) in Sertoli cells.
Terla Muir; Ingrid Sadler-Riggleman; Jeffrey D Stevens; Michael K Skinner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Molecular reproduction and development     Volume:  73     ISSN:  1040-452X     ISO Abbreviation:  Mol. Reprod. Dev.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-01-31     Completed Date:  2007-03-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8903333     Medline TA:  Mol Reprod Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  491-500     Citation Subset:  IM    
Copyright Information:
Copyright 2006 Wiley-Liss, Inc.
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA.
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MeSH Terms
Cell Differentiation / physiology*
Cells, Cultured
DNA-Binding Proteins / biosynthesis,  genetics,  physiology*
Down-Regulation / physiology
Follicle Stimulating Hormone / physiology*
Growth Inhibitors / antagonists & inhibitors
Helix-Loop-Helix Motifs / physiology*
Inhibitor of Differentiation Protein 1 / antagonists & inhibitors,  physiology
Organ Specificity / physiology
Sertoli Cells / cytology*,  metabolism,  physiology*
Transcription Factors / biosynthesis,  genetics,  physiology*
Transferrin / genetics
Two-Hybrid System Techniques
Up-Regulation / physiology*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Growth Inhibitors; 0/ID1 protein, rat; 0/Inhibitor of Differentiation Protein 1; 0/Tcf4 protein, rat; 0/Transcription Factors; 11096-37-0/Transferrin; 9002-68-0/Follicle Stimulating Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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