Growth hormone-mediated transcriptional activation of the rat serine protease inhibitor 2.1 gene involves both interleukin-1 beta-sensitive and -insensitive pathways

Le Cam, A Paul, Claudine [UCL] Thissen, Jean-Paul [UCL]

Growth hormone (GH)-dependent activation of the rat serine protease inhibitor 2.1 (spi 2.1) gene in vivo requires both a modification of the chromatin structure and the activation of transcription factors mediated by the tyrosine protein Janus kinase JAK2. To address the question of the relationship between those two GH effects, we used interleukin 1 beta (Il-1 beta) that was previously shown to inhibit spi 2.1 gene expression. In cultured hepatocytes from normal rats, Il-1 beta did not antagonize GH-dependent stimulation of promoter activity (i.e., in episomal constructs) mediated by transcription factors activated by JAK2. In hepatocytes from inflamed rats, GH triggered JAK2-dependent activation of transcription factors as in control cells but failed to stimulate genomic spi 2.1 gene expression. It thus appears that the Il-1 beta-insensitive activation of transcription factors by GH is independent of its action on the nucleosomal structure of the spi 2.1 gene which, in contrast, is sensitive to this cytokine. (C) 1998 Academic Press.