2-methoxyestrone and 2-methoxyestriol

To clarify the mechanism of action of catecholestrogen and catecholestrogen 2-monomethylether on lipid metabolism, the effects of 2-OHE1, 2-MeoE1, 2-MeoE3 and E2-17 beta on serum total cholesterol, HDL-cholesterol, triglyceride levels, beta/alpha lipoprotein ratio, body weights and uterine weights were investigated in five serial experimental systems using normochoesterolemic and dietary hypercholesterolemic female rats those were previously oophorectomized. The results obtained were as follows: 1) In a short term hormone administration experiment using normocholesterolemic rats, 2-OHE1, 2-MeoE1, and 2-MeoE3 showed a serum triglyceride reducing effect as strong as that of E2-17 beta. 2) To integrate the results of the short term hormone administration experiment in normocholesterolemic rats and the results of short term and long term hormone administration experiments in dietary hypercholesterolemic rats, the serum cholesterol reducing activity was in the following sequences; 2-MeoE3 not equal to E2-17 beta greater than 2-MeoE1 greater than 2-OHE1. Hypocholesterolemic activity of 2-MeoE3 was almost equivalent or slightly stronger than that of E2-17 beta, and 2-MeoE1 showed approximately a half of that of E2-17 beta. 3) According to the results of the short term hormone administration experiment, and the long term hormone administration experiment in dietary hypercholesterolemic rats, the serum HDL-cholesterol increasing effect was in the following relation; E2-17 beta greater than 2-MeoE3 greater than 2-MeoE1. Dose dependency was not observed in the serum HDL-cholesterol increasing effect. 4) From the results of the short term hormone administration experiment, 2-MeoE3 had an equal or stronger activity than that of E2-17 beta in serum beta/alpha lipoprotein ratio decreasing effect. 5) In experiment 4 which 2-MeoE3 and E2-17 beta were administered singly or combined with Tamoxifen to the dietary hypercholesterolemic rats, the hypocholesterolemic effect of neither hormone was inhibited by Tamoxifen. On the other hand, the uterotrophic activity of E2-17 beta was slightly, but not significantly inhibited by Tamoxifen. 6) Although E2-17 beta, 2-MeoE1 exhibited a remarkable uterotrophic activity and a slight reducing effect on body weight, neither 2-OHE1 nor 2-MeoE3 had an effect on uterine weight or body weight. Given these results, it was strongly suggested that the effects of catecholestrogen and catecholestrogen 2-monomethyl ether on serum lipids were not m

Topics: Animals; Cholesterol; Cholesterol, HDL; Diet; Estradiol; Estriol; Female; Hydroxyestrones; Hypercholesterolemia; Ovariectomy; Rats; Rats, Inbred Strains; Triglycerides

Topics: Animals; Cholesterol; Estriol; Estrone; Female; Hydroxyestrones; Hypercholesterolemia; Lipoproteins; Rats; Rats, Inbred Strains

The hypocholesterolemic effect of 2-methoxyestrone (2-MeOE1), 2-methoxyestriol (2-MeOE3) and estradiol-17 beta (E2-17 beta) was investigated in two experimental systems of normocholesterolemic and dietary hypercholesterolemic rats that had undergone oophorectomy. Each compound was subcutaneously administered for 6 consecutive days at a dose of 10 micrograms per day in the former systems and at 300 micrograms per day in the latter system, respectively. The hypocholesterolemic effect was in the following relation: 2-MeOE3 = E2 - 17 beta greater than 2-MeOE1. In the latter system, the serum total cholesterol level of individual rats in both 2-MeOE3- and E2-17 beta-administered groups returned to normal. No uterotrophic activity was exhibited by either 2-MeOE1 or 2-MeOE3, while E2-17 beta exhibited an anomalous activity. The effect of 2-MeOE1 and 2-MeOE3 on body weight was not exhibited, while E2-17 beta reduced it slightly. The results suggest that catechol estrogen 2-monomethyl ether plays an important role in lipid metabolism through estrogen receptor independent mechanisms and has a pharmacologically important effect on hyperlipidemia and atherosclerosis.

Topics: Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Estradiol; Estriol; Estrone; Female; Hydroxyestrones; Organ Size; Rats; Rats, Inbred Strains; Uterus