Rapid Events in Growth Hormone Action. Induction of c-fos and c-jun Transcription in 3T3-F442A Preadipocytes*

Abstract

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.

Dual Regulation of Phosphorylation and Dephosphorylation of C/EBPβ Modulate Its Transcriptional Activation and DNA Binding in Response to Growth Hormone

“…The subsequent dephosphorylation is better timed to contribute to the termination of c-fos promoter activation. Rapid and transient activation of c-fos expression is characteristic of this early-response gene in response to GH and many growth factors (35,55,56), and characteristically subsides within 60 min.…”

Growth Hormone Regulates Phosphorylation and Function of CCAAT/Enhancer-binding Protein β by Modulating Akt and Glycogen Synthase Kinase-3

“…The stimulation of Akt by GH subsided from 15 to 60 min (Fig. 2, A, B, and C, upper panels, lanes [3][4][5][6]. The lower panels show total Akt.…”

“…Analysis of the regulation of gene transcription by GH has provided additional insight into signaling mechanisms between the GH receptor (GHR) and nuclear events regulating transcription (3,4). Regulation of the expression of the proto-oncogene c-fos has served as a useful model for studying regulation of gene expression by GH (5,6), and has demonstrated diverse effects of GH on the phosphorylation of transcription factors. For example, GHstimulated tyrosine phosphorylation of STATs and serine phosphorylation of Elk-1 are required for these transcription factors to activate transcription of c-fos in response to GH (7)(8)(9)(10)(11)(12)(13).…”

Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein β in GH-stimulated c-fos expression

“…The proto-oncogene c-fos, which participates in cellular proliferation and differentiation (Holt et al 1986, Nishikura & Murray 1987, is rapidly and transiently induced by GH (Doglio et al 1989, Gurland et al 1990 as well as by other stimuli. Analysis of c-fos provides a model for understanding mechanisms of GH-regulated gene transcription (Cesena et al 2007).…”