Prolactin enhances CCAAT enhancer-binding protein-beta (C/EBP beta) and peroxisome proliferator-activated receptor gamma (PPAR gamma) messenger RNA expression and stimulates adipogenic conversion of NIH-3T3 cells.
Extracellular stimuli trigger adipocyte differentiation by inducing the complex cascades of transcription. Transcription factors CCAAT enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARgamma) play crucial roles in this process. Although ectopic expression of these factors in NIH-3T3 cells, a multipotential mesenchymal stem cell line, results in adipogenic conversion, little is known as to hormonal factors that regulate adipogenesis in these cells. In this report we demonstrate that PRL, a lactogenic hormone, enhances C/EBPbeta and PPARbeta mRNA expression and augments adipogenic conversion of NIH-3T3 cells. Moreover, we show that ectopic expression of the PRL receptor in NIH-3T3 cells results in efficient adipocyte conversion when stimulated with PRL and a PPARgamma ligand, as evidenced by expression of the adipocyte differentiation-specific genes as well as the presence of fat-laden cells. We further demonstrate that signal transducer and activator of transcription 5 (Stat5), a PRL signal transducer, activates aP2 promoter in a PRL-dependent manner. These results suggest that PRL acts as an adipogenesis-enhancing hormone in NIH-3T3 cells.
Nanbu-Wakao
R
R
Helix Research Institute, Chiba, Japan.
Fujitani
Y
Y
Masuho
Y
Y
Muramatu
M
M
Wakao
H
H
D016475:3T3 Cells / Q000187:drug effects / Q000473:pathology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D051379:Mice; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014970:Xanthines / Q000494:pharmacology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D014970:Xanthines; C058490:1-methyl-3-butylxanthine; D003907:Dexamethasone; D011388:Prolactin