Growth Hormone-Mediated Transcriptional Activation of the Rat Serine Protease Inhibitor 2.1 Gene Involves Both Interleukin-1 β-Sensitive and -Insensitive Pathways

Growth hormone (GH)-dependent activation of the rat serine protease inhibitor 2.1 (spi2.1) genein vivorequires 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 β (Il-1 β) that was previously shown to inhibitspi2.1 gene expression. In cultured hepatocytes from normal rats, Il-1 β 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 genomicspi2.1 gene expression. It thus appears that the Il-1 β-insensitive activation of transcription factors by GH is independent of its action on the nucleosomal structure of thespi2.1 gene which, in contrast, is sensitive to this cytokine.