Sex difference in the saturable binding of low-density lipoprotein by liver membranes in ageing rats

It is well documented that women of child-bearing age tend to have lower serum low-density lipoprotein (LDL) concentrations than men. In order to explore the metabolic basis of this sex difference, we have compared the saturable binding of 125I-labeled LDL (d 1.02-1.05 g/ml) at 37 degrees C by liver membranes from healthy male and female Wistar rats of different ages (15-213 days). Woolf plots of saturable binding curves over the concentration range 15-65 micrograms LDL protein/ml were linear and compatible with a single class of binding sites. Maximum binding capacity (Bmax) was not significantly different in male and female animals of 15-19 days of age (respectively, 0.331 +/- 0.018 vs. 0.427 +/- 0.044 micrograms LDL protein/mg membrane protein, mean +/- S.E.). Thereafter, Bmax increased in females, reaching a peak of 0.635 +/- 0.042 micrograms LDL protein/mg membrane protein at 60 days. As no increase in Bmax occurred in males, values were significantly higher (P less than 0.02) in females than in males (by a mean of 61-117%) at all ages after 30 days. During ageing, serum cholesterol concentration changed reciprocally with Bmax in females (Pearson's correlation coefficient, r = -0.761, P less than 0.01) and remained essentially constant in males. The equilibrium dissociation constant for 125I-labelled LDL binding to the hepatic membranes was unaffected by both age and sex. These results provide evidence that the sex difference in the plasma total and LDL cholesterol concentrations is related, at least in part, to a greater mean LDL receptor density in the livers of females.