Estrogen markedly increases LDL-receptor activity in hypercholesterolemic patients.

We investigated the change in low-density lipoprotein receptor activity following the administration of estrogen to patients with hypercholesterolemia (HC). Studies were conducted in 16 patients with HC (total cholesterol (TC)>220 mg/dL) and 133 healthy control subjects. LDL-R activity was measured by fluorocytometry. Three of sixteen patients with HC showed low LDL-R activity below 80% together with extremely high serum levels of TC and LDL cholesterol (LDL-C). LDL-R activity showed an inverse correlation with serum levels of TC and LDL-C (p<0.05, respectively). Two women with initially low LDL-R activity who showed a marked increase in LDL-R activity exhibited a normalized activity at four and eight weeks after estriol administration, proportional to the reduction in serum levels of TC and LDL-C. One man with an initially extremely low LDL-R activity showed no abnormality at the sites of exons 7, 14, 17 and intron 12 by the PCR-DGGE method, which are common sites for point-mutations of LDL-R among Japanese patients with HC. Estrogen reduced serum levels of TC and LDL-C in patients with HC, at least in part, via an increase in the LDL-R activity of patients with HC and an initially low LDL-R activity.