Independent responsiveness of frog liver low-density lipoprotein receptor and HMGCoA reductase to estrogen treatment

Cholesterol metabolism in the female frog exhibits circannual modifications which parallel plasma estrogen fluctuations. Estrogens enhance production and lipidation of the yolk precursor vitellogenin by inducing the transcription of its gene and by stimulating the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. The time dependence of the effects that these hormones have on HMGCoA reductase and the low-density lipoprotein (LDL) receptor in the liver of Rana esculenta complex has been investigated. Following estrogen treatment, the levels of LDL receptor mRNA and protein gradually increased, with a maximum concentration observed at 3 days. The HMGCoA reductase protein level increased progressively, while the mRNA level was not significantly modified. Thus the LDL receptor and HMGCoA reductase in frog behave independently after estrogen stimulation, as already reported to occur in the rat. This suggests a uncoordinated regulation that might be even partially related with the changes in cellular cholesterol content

Independent behaviour of rat liver LDL receptor and HMGCoA reductase under estrogen treatment.

The main molecules of hepatic cholesterol homeostasis are HMGCoA reductase, the key enzyme of the biosynthetic pathway, and LDL receptor, responsible for the uptake of plasma lipoproteins. Estrogens are reported to cause hypolipidemia in mammalians inducing hepatic LDL receptor. The effect of such hormones on HMGCoA reductase is very ambiguous. The mechanism and the time-dependence of the effects of these hormones on HMGCoA reductase and LDL receptor in rat liver have been investigated at mRNA and protein levels, at different times after estrogen administration. Estrogens cause an early increase of LDLr, at both mRNA and protein level, and an increase of HMGCoA reductase, just at protein level, detectable only after 5 days. The independent behavior of LDLr and HMGCoA reductase under estrogen treatment suggests a not coordinate regulation by these hormones