Relation of growth- and sterol-related regulatory pathways for low density lipoprotein receptor gene expression.

The relationship between growth- and sterol-related regulation of low density lipoprotein (LDL) receptor gene expression was examined in human skin fibroblasts. Platelet-derived growth factor (PDGF) and high density lipoprotein (HDL3) each produced increased cellular LDL protein and mRNA levels. However, HDL, when added with PDGF or insulin produced no additional effect. Coincubations with 25-hydroxycholesterol markedly attenuated fibroblast LDL receptor protein and mRNA response to growth activation. Acute transfection experiments using sterol-responsive elements of the LDL receptor gene indicated that these elements are also responsive to growth activation with PDGF. These data indicate that alteration of cellular sterol balance or metabolism leading to release of end product repression contributes to growth-related stimulation of LDL receptor gene expression.