Low‐density‐lipoprotein‐receptor mRNA content of fibroblasts from normal and familial hypercholesterolaemic subjects

The amount of mRNA for the low‐density‐lipoprotein (LDL) receptor in cultured human fibroblasts was estimated by hybridization of the poly(A)‐rich RNA fraction with a DNA probe, using the recovery of β‐actin mRNA to correct for losses. During incubation of the cells with lipoprotein‐deficient serum (LPDS) both the LDL‐receptor mRNA content and the rate of receptor protein synthesis increased fourfold during the first 16 h and then fell by approximately 50% during the next 24 h. The content of β‐actin mRNA fell by a similar amount, so that the ratio of receptor/β‐actin mRNAs rose and then remained constant. The fall in β‐actin mRNA content during incubation with LPDS was not prevented by the addition of cholesterol to the medium. In cells from a homozygous familial hypercholesterolaemic (FH) subject that bound 20% of the normal amount of LDL, the content of LDL‐receptor mRNA and the changes during incubation with LPDS or free sterols were similar to normal. Cells from a familial hypercholesterolaemic subject that produced no immunodetectable receptor protein produced a small amount of receptor mRNA of apparently normal size which responded in the same way as in normal cells to LPDS and free sterols.