Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter.
Activin A is a potent growth and differentiation factor related to transforming growth factor beta. In somatotrophs, activin suppresses the biosynthesis and secretion of growth hormone (GH) and cellular proliferation. We report here that, in MtTW15 somatotrophic tumor cells, activin decreased GH mRNA levels and inhibited expression of transfected GH promoter--chloramphenicol acetyltransferase fusion genes. Deletion mapping of nucleotide sequences mediating this inhibition led to the identification of a region that has previously been characterized as binding the pituitary-specific transcription factor Pit-1/GHF-1. Characterization of nuclear factor binding to this region demonstrated that binding of Pit-1 to the GH promoter is lost on activin treatment. These results indicate that activin-induced repression of GH biosynthesis is mediated by the loss of tissue-specific transcription factor binding to the GH promoter and suggest a possible general mechanism for other activin responses, whereby activin regulates the function of other POU- or homeodomain-containing transcription factors.
Struthers
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RS
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
Gaddy-Kurten
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Vale
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WW
D028341:Activins; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics*; D066298:In Vitro Techniques; D007265:Inhibins / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000494:pharmacology; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C494186:Pou1f1 protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D028341:Activins; D007265:Inhibins; D013006:Growth Hormone