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

Growth hormone (GH)-dependent activation of the rat serine protease inhibit or 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 tyro sine 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 hepato cytes from normal rats, Il-1 beta did not antagonize GH-dependent stimulati on of promoter activity (i.e., in episomal constructs) mediated by transcri ption factors activated by JAK2. In hepatocytes from inflamed rats, GH trig gered JAK2-dependent activation of transcription factors as in control cell s 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 .