Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes.
To investigate early events in GH action, we examined whether GH altered the expression of c-fos and c-jun mRNA in 3T3-F442A cells. The rapid induction of these early response protooncogenes is one of the initial events in stimulation of cell proliferation and differentiation by a variety of growth factors. In 3T3-F442A preadipocytes, which differentiate in response to GH, treatment with GH for 15-30 min transiently increased the expression of c-fos and c-jun mRNA at GH concentrations in the physiological range (10-500 ng/ml). Both genes were superinduced by GH in the presence of cycloheximide. Nuclear run-on experiments indicated that the effect of GH on c-fos and c-jun occurred at the level of gene transcription, indicating that in the 3T3-F442A preadipocytes, GH acts similarly to other growth factors which induce c-fos and c-jun. Chronic preincubation with the phorbol ester phorbol 12-myristate 13-acetate interfered with the induction of c-fos by GH, suggesting that diacylglycerol and protein kinase C are involved in this effect of GH. Insulin-like growth factor-I and insulin were less effective than equimolar concentrations of GH in inducing c-fos expression. Taken together, these findings are consistent with coordinated expression of c-fos and c-jun playing an early role in responses to GH in 3T3-F442A cells.
Gurland
G
G
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Ashcom
G
G
Cochran
B H
BH
Schwartz
J
J
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; D007328:Insulin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate