Abstract
17β-Estradiol (E2) has long been known for protecting against coronary heart disease by lowering cholesterol levels in premenopausal women. A recent study in our laboratory suggested that two hydroxylated metabolites of E2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estrogen metabolites in ovariectomized rats with a view toward mimicking the true postmenopausal situation in humans. Their effects in reproductive tissues were also evaluated histologically. Fundamentally, the following issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved without eliciting estrogenic activities on reproductive tissues? The results of this investigation showed that a number of oxygenated metabolites of estradiol can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a striking hypocholesterolemic effect and a substantial uterotropic effect. 2-Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2-meoE1) produced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects.
Footnotes
-
Send reprint requests to: Kenneth A. Bachmann, Ph.D., F.C.P., Distinguished University Professor and Chair, Department of Pharmacology, The University of Toledo, College of Pharmacy, 2801 W. Bancroft Street, Toledo, OH 43606. E-mail:kbachma{at}utnet.utoledo.edu
- Abbreviations:
- E2
- 17β-estradiol
- ER
- estrogen receptor
- 2-OHE2
- 2-hydroxyestradiol
- 4-OHE2
- 4-hydroxyestradiol
- 2-meoE1
- 2-methoxyestrone
- 2-meoE2
- 2-methoxyestradiol
- TAM
- tamoxifen
- 4-OHT
- 4-hydroxytamoxifen
- LDL
- low density lipoprotein
- TCL
- total cholesterol level
- CYP
- cytochrome P450
- CAD
- coronary artery (or heart) disease
- OVX
- ovariectomized
- AEBS
- antiestrogen binding sites
- Received August 19, 1997.
- Accepted March 31, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|