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 com plex cascades of transcription. Transcription factors CCAAT enhancer-bindin g proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (P PAR gamma) play crucial roles in this process. Although ectopic expression of these factors in NIH-3T3 cells, a multipotential mesenchymal stem cell l ine, results in adipogenic conversion, little is known as to hormonal facto rs that regulate adipogenesis in these cells. In this report we demonstrate that PRL, a lactogenic hormone, enhances C/EBP beta and PPAR gamma mRNA ex pression and augments adipogenic conversion of NIH-3T3 cells. Moreover, we show that ectopic expression of the PRL receptor in NIH-3T3 cells results i n efficient adipocyte conversion when stimulated with PRL and a PPAR gamma ligand, as evidenced by expression of the adipocyte differentiation-specifi c genes as well as the presence of fat-laden cells. We further demonstrate that signal transducer and activator of transcription 5 (Stat5), a PRL sign al transducer, activates aP2 promoter in a PRL-dependent manner. These resu lts suggest that PRL acts as an adipogenesis-enhancing hormone in NIH-3T3 c ells.