Correlation of Hepatic Estrogen Receptor Concentrations and Estrogen-Mediated Elevation of Very Low Density Lipoproteins

After 2 weeks of administration of 17β-estradiol (E2; ∼20–30 Mg E2/kg BW-day) to adult ovariectomized female rats, concentrations of circulating triglycerides were increased 3- to 4-fold with no apparent effect on serum cholesterol levels. The increase in serum triglycerides was confined to the very low density lipoprotein (VLDL) fraction. It was determined that exposure to E2 for longer than 3 days was required to elicit this response. The concentrations of cytosolic and nuclear receptors were measured by Scatchard analysis, after either 7 or 14 days of estrogen treatment. Redistribution of hepatic estrogen receptors from the cytosolic to the nuclear compartment was not observed in animals continuously exposed to estrogen, although elevations in the concentrations of triglycerides associated with VLDL were apparent at the time points examined. Previous investigations have shown that after hypophysectomy, the concentrations of hepatic estrogen receptors are significantly decreased. We have confirmed this finding and have further shown that the nuclear uptake of cytosolic receptors is less in hypophysectomized animals than in controls when evaluated in a cellfree system. Similarly, nuclear concentrations of estrogen receptors after estrogen treatment in vivo are considerably less in hypophysectomized animals than in controls. Hypophysectomy abolished the response of the liver to estrogen; concentrations of circulating triglycerides associated with VLDL were unaffected in estrogen-treated hypophysectomized animals. These findings suggest that a correlation exists between the amount of hepatic cytosolic receptors and estrogen-mediated responses of liver.