1989 Volume 6 Issue 1 Pages 49-56
To compare the hypocholesterolemic effect and other biological activities of 2-methoxyestriol (2-MeOE3) and estradiol-17β (E2-17β), osmotic minipumps (transporting rate at 37°C, 0.5μl propylene glycol/h) containing these hormone solutions at either of 2 concentrations, 3mg/ml (36μg/day administration, “low dose”) and 30mg/ml (360μg/day administration, “high dose”) were implanted subcutaneously into previously oophorectomized female rats which were fed a diet containing 1% cholesterol. Blood sampling and measurement of body weight were carried out at one-week intervals for 4 weeks after the minipump implantation. Following the last blood sampling all animals were killed. The serum cholesterol was determined by an enzymatic method.
Unlike E2-17β, 2-MeOE3 exerted little uterotrophic effect and had no effect on body weight even at a high dose. The serum total cholesterol level in low- and high-dose 2-MeOE3 groups exhibited 35.8-46.8% and 47.1-72.2% reductions, respectively, compared with the corresponding control values (administered vehicle alone), while the respective reductions in the E2-17β groups were 5.7-45.1% and 26.0-79.1%. The serum HDL-cholesterol level in the low dose E2-17β group showed significantly higher levels in the 1st and 3rd weeks, and the high-dose E2-17β group, in the 1st, 2nd, and 3rd weeks, compared with the corresponding control values. The high-dose 2-MeOE3 group also exhibited a significantly higher level in the 1st week. These results suggest that 2-MeOE3 lowers serum cholesterol by enhancing not only its catabolism and excretion in the liver, but also by lipoprotein synthesis, and that, unlike the case for E2-17β, the mechanism of action of this hormone involves no estrogen receptors.
