Effects of estradiol-17beta on cholesterol metabolism in the rat: a study using a deuterium label and mass spectrometry.
The effect of estradiol-17beta (E2) on several important aspects of cholesterol metabolism were examined in the rat. Ovariectomized rats were implanted subcutaneously with 1 or 4 cm. of silastic tubing packed with E2, and were also given 2% D2O in their drinking water. The E2 diffused slowly out of the implants and the two different lengths of tubing resulted in constant E2 blood concentrations of either high (4.0 cm) or physiological (1.0 cm) levels. By measuring the rate of incorporation of deuterium into plasma cholesterol by mass spectrometry over a period of 42 days, we determined the rate constant of cholesterol synthesis and cholesterol turnover time and rate under two E2 dosage conditions. E2 treatment did not affect the rate constant of cholesterol turnover rate (mg synthesized/day) showed a dose dependent reduction with increasing doses of E2. This may be secondarily caused by E2's suppression of both food intake and subsequent weight gain; E2 treated animals are smaller and, therefore, synthesize less cholesterol per day. Additionally, E2 treated animals showed a rise in plasma cholesterol levels and in the fraction of labeled cholesterol appearing in the plasma.
D000818:Animals; D002369:Castration; D002784:Cholesterol / Q000097:blood*; D003903:Deuterium; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D013058:Mass Spectrometry; D051381:Rats; D013997:Time Factors
D004958:Estradiol; D002784:Cholesterol; D003903:Deuterium