Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover.
Growth hormone (GH) is required for the terminal differentiation of preadipose Ob1771 cells that have entered the differentiation program as evidenced by the expression of early marker genes (pOb24 and lipoprotein lipase). Induction of c-fos mRNA within 15 min and induction of insulin-like growth factor I mRNA within a few hours take place in response to GH. The role of GH is mediated, at least in part, by means of the activation of protein kinase C, as shown by the inhibition of epidermal growth factor binding and by the expression of the c-fos gene, and is thus analogous to the action of prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate in this respect. However, in contrast to that of the c-fos gene, the regulation of insulin-like growth factor I gene expression by GH is not mediated by means of the activation of protein kinase C, and, in line with this, prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate were ineffective. GH and prostaglandin F2 alpha were able to stimulate the formation of diacyglycerol within a few seconds, but GH did not elicit an accumulation of inositol phosphates, in contrast to that generated by prostaglandin F2 alpha. We conclude that the transduction signal of GH action in c-fos mRNA induction is the formation of diacylglycerol and that the mechanism whereby GH can activate protein kinase C is associated with a phospholipase C-mediated hydrolysis of glycerophospholipids other than inositol phospholipids.
Doglio
A
A
Laboratoire de Bactériologie-Virologie, Faculté de Médecine, Chemin de Vallombrose, Nice, France.
Dani
C
C
Grimaldi
P
P
Ailhaud
G
G
D000818:Animals; D002460:Cell Line; D013006:Growth Hormone / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*
D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D007294:Inositol; D013006:Growth Hormone; D011493:Protein Kinase C