Transcriptional control of the expression of lipoprotein lipase gene by growth hormone in preadipocyte Ob1771 cells.

Abstract

A direct and modulating effect of growth hormone (GH) on the regulation of the lipoprotein lipase (LPL) gene has been shown in preadipocyte Ob1771 cells. Growth hormone acts as a modulator within the physiological range of concentrations and regulates the abundance of the two species of LPL mRNAs (3.3 and 3.7 kb) in a differentiation-dependent manner, the stimulation factor being between 4- and 7-fold. The regulation of LPL gene expression by GH is rapid (2 to 8 h) and similar for both mRNA species. It is reversible and takes place primarily at a transcriptional level. Parallel increases of LPL mRNAs, LPL protein, and LPL activity are observed. The expression of both cellular and secreted activities is stimulated by GH. The role of GH is mediated, at least in part, by means of activation of protein kinase C. In the presence of 4-beta-phorbol-12-myristate 13-acetate (PMA), a parallel increase of LPL mRNA content and LPL activity is observed at half the values obtained upon stimulation by GH. The kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) abolishes completely the PMA-induced accumulation but decreases only by half that induced by GH. Like H7, staurosporine, polymixin B, and sphingosine inhibit only by half the stimulatory effect of GH on the expression of the LPL gene. These results show for the first time a rapid regulation of the LPL gene expression at a transcriptional level. Ob1771 cells should be helpful in gaining some insights in the promoter function of the LPL gene and the trans-acting factors involved in its regulation.