Endocrine Abstracts

Hypercholesterolemia is associated with athero-thrombotic disease, a leading cause of mortality worldwide. Advances in both dietary and pharmacological interventions contribute to prevention and treatment of modifiable risk factors.Purified soybean phytoestrogens, isoflavones genistein (GEN) and daidzein (DAI), were reported to exert moderate cholesterol-lowering effect. In this research first we studied age-related modifications in hepatic cholesterol metabolism and serum estradiol concentration of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes. Serum and hepatic total cholesterol (TCH), bile acid and cholesterol precursors were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered GEN or DAI (35 mg/kg per daily during four weeks) to MA rats were evaluated vs vehicle (sterile olive oil) – treated MA females. After decapitation, perfused rat livers and serum were used to determine total cholesterol (TCH), its oxidative metabolites (7α-, 27- and 24-hydroxycholesterol) and precursors (lanosterol, desmosterol, dihydro-lano sterol and lathosterol), using gas chromatography/mass spectrometry. Serum estradiol was determined by ECLIA. MA IC females were characterized by: higher (P<0.05) serum TCH, lower (P<0.05) hepatic TCH and its biosynthetic precursors, lower (P<0.05) hepatic7α-hydroxycholesterol but elevated (P<0.05) 27- and 24- hydroxycholesterol in comparison to YA IC. Both GEN and DAI decreased (P<0.05) hepatic 27-hydroxycholesterol, with no effect on any other parameter of cholesterol metabolism. We obtained age-related reduction of serum estradiol, which was reversed by both soybean phytoestrogens. In conclusion, age-related dyslipidemia was associated with reduced 7α-hydroxycholesterol, main intermediate of neutral pathway, and higher 27—hydroxycholesterol, main intermediate of alternative acidic pathway of Chol degradation to bile acid. Both GEN and DAI lowered hepatic 27- hydroxycholesterol, which might be associated with elevated serum estradiol concentrations. Further research is needed to examine this possibility.