Tissue-specific regulation of low density lipoprotein receptor gene expression.

LDL receptor mRNA levels are increased by mitogenic stimulation of PBMC and are less effectively regulated by exogenous LDL in the activated cells. Enhanced LDL receptor mRNA levels reflect increased rates of gene transcription and not stabilization of mRNA. The alteration of LDL-mediated regulation of LDL receptor gene expression in mitogen-activated PBMC is not the result of cellular proliferation alone and occurs without apparent changes in measurable regulatory pools of cholesterol. These results indicate that signals transduced during mitogenic stimulation, as well as ambient LDL concentration, play a major role in regulating LDL receptor gene transcription. Fibroblasts apparently differ from PBMC in the effect of modulatory proteins on LDL receptor mRNA levels. In fibroblasts, LDL receptor gene transcription appears to be down-regulated by a short-lived protein whereas the dominant regulatory influence in PBMC appears to be a short-lived protein with a positive effect on transcription. Differences in the expression of specific transcription factors may contribute to cell-specific alterations in the regulation of LDL receptor gene expression by lipids.