Effects of 2-fluoroestradiol on lipid metabolism in the ovariectomized rat.
Biological activities of estrogen molecules are altered by fluorination of ring A, and the resulting impairment to form catechols. 2-fluoroestradiol (2-F-E2) has been found to be devoid of carcinogenic action despite its high estrogenic potency; its metabolic effects are so far unknown. This study was designed to investigate the effects of 2-F-E2 on lipid metabolism, as compared to those of estradiol-17 beta(E2). Ovariectomized rats received E2 or 2-F-E2 by s.c. injection at a dose of 60 micrograms for three consecutive days. Parameters measured were weights of parametrial fat depots, fat cell volumes, levels of triacylglycerol and acylcholesterol in plasma, and enzymatic responses to the estrogens in isolated parametrial fat cells as evaluated in terms of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities. 2-F-E2 and E2 were found to produce comparable decreases in fat depots, cell volumes and plasma levels of acylcholesterol whereas plasma triacylglycerol was unchanged. Both estrogens decreased LPL, and increased HSL activities to the same extent. Thus, 2-F-E and E2 exhibited comparable effects on lipid metabolism. These effects appeared to depend mainly on the estrogenic potency of these molecules, and to be distinct from their carcinogenic action. Despite its high estrogenic potency, 2-F-E2 was found to be slightly less estrogenic than E2.
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; C037475:2-fluoroestradiol; D004958:Estradiol; D002784:Cholesterol; D008049:Lipase