Growth hormone suppression of insulin-like growth factor binding protein-1promoter activity

Hepatic transcription of insulin-like growth factor binding protein-1 (IGFB P-1) is rapidly downregulated by growth hormone (GH) which is also known to induce expression of c-fos and c-jun. Go-expression of c-fos or c-jun in r at hepatocytes, individually or together, suppresses IGFBP-1 promoter activ ity by approximate to 60%. When hepatic nuclear extracts from sham-operated , hypophysectomized (hypox) and GH-treated hyper rats were analyzed by DNas e-l footprinting, differences in the protection pattern were identified in three regions of the IGFBP-1 promoter. F1 corresponding to - 660 to - 640 b p showed acute changes in response to GH administration. In additional regi ons, F2 and F3, representing - 758 to - 748 bp and - 477 to - 447 bp; respe ctively, differences were apparent between nuclear extracts from the hyper and sham-operated rats. When F1 and F2 were removed by deletion of the regi on from - 824 to - 557 bp, the GH response was lost but suppression by co-e xpression of c-fos and c-jun was preserved. A putative AP-1 binding site wa s present in the F3 footprint region, however removal of F3 did not affect the GH responsiveness. These data indicate that several distinct sequences, other than the putative AP-1 site are involved in mediating the GH effects on IGFBP-1 transcription. (C) 1999 Elsevier Science Ireland Ltd. All right s reserved.