Hypoalbuminemia is accompanied by
hypercholesterolemia in both
nephrotic syndrome and hereditary analbuminemia.
Hypercholesterolemia is more severe in the female than in the male
Nagase analbuminemic rats (NAR). The sex difference in plasma
cholesterol diminishes after
ovariectomy (OVX) and reappears after
estrogen replacement in the NAR. The molecular mechanism responsible for the sex difference in severity of
hypercholesterolemia in NAR is not known and was investigated here. To this end, hepatic hydroxylmethylglutaryl (
HMG)-CoA reductase,
cholesterol 7alpha-hydroxylase, and
LDL receptor were determined in male, female, and OVX female NAR and Sprague-Dawley (SD) rats. Plasma
cholesterol,
triglycerides, and hepatic
HMG-CoA reductase activities were greater in both female and male NAR than in SD rats. This was coupled with upregulation of
cholesterol 7alpha-hydroxylase in both male and female NAR compared with SD controls.
LDL receptor in male NAR was similar to that in male SD rats but was significantly reduced in female NAR. OVX partially, but significantly, reduced plasma
cholesterol and
triglyceride levels in female NAR. This was coupled with a significant rise in hepatic
cholesterol 7alpha-hydroxylase and a modest increase in hepatic
LDL receptor. In contrast, OVX resulted in a mild elevation of plasma
cholesterol and no significant changes in total hepatic
HMG-CoA reductase,
cholesterol 7alpha-hydroxylase, or
LDL receptor in female SD rats. Thus the greater severity of
hypercholesterolemia in the female NAR appears to be due, in part, to a combination of the constrained compensatory upregulation of
cholesterol 7alpha-hydroxylase and
LDL receptor deficiency.