Multiple mechanisms of growth hormone-regulated gene transcription.

Diverse physiological actions of growth hormone (GH) are mediated by changes in gene transcription. Transcription can be regulated at several levels, including post-translational modification of transcription factors, and formation of multiprotein complexes involving transcription factors, co-regulators and additional nuclear proteins; these serve as targets for regulation by hormones and signaling pathways. Evidence that GH regulates transcription at multiple levels is exemplified by analysis of the proto-oncogene c-fos.

Endogenous CCAAT/enhancer binding protein beta and p300 are both regulated by growth hormone to mediate transcriptional activation.

The regulation of c-fos transcription by GH involves multiple factors, including CCAAT/enhancer binding protein (C/EBP) beta. Knockdown of C/EBPbeta by RNA interference prevents stimulation of endogenous c-fos mRNA by GH, indicating a key role for C/EBPbeta in GH-stimulated c-fos transcription. GH rapidly increases the occupancy of both endogenous C/EBPbeta and p300 on the c-fos promoter in 3T3-F442A preadipocytes as indicated by chromatin immunoprecipitation.