Regulation of LDL receptor mRNA levels in human lymphocytes by functional demand and ambient sterols.

Mitogenic stimulation increases lymphocyte LDL receptor gene expression. Increases are dependent on protein synthesis, not explained by altered mRNA stability and subject to negative feedback regulation. Furthermore, transcription occurs for at least 24 hr and requires ongoing protein synthesis. Depletion of putative endogenous pools of cholesterol that regulate cellular sterol metabolism cannot account for the increase in LDL receptor gene expression caused by mitogenic stimulation. Mitogen-stimulated cells always contain substantially higher levels of LDL receptor messenger RNA than corresponding resting cells. Mitogenic stimulation thus provides a signal that increases LDL receptor gene expression over and above that predicted from the concentration of exogenous sterols. These studies, therefore, indicate that LDL receptor transcription is modulated by signals transduced during cellular activation as well as by negative feedback from regulatory sterols.