This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lundeen, S. G. Articles by Winneker, R. C. Search for Related Content PubMed PubMed Citation Articles by Lundeen, S. G. Articles by Winneker, R. C.

Characterization of the Ovariectomized Rat Model for the Evaluation of Estrogen Effects on Plasma Cholesterol Levels

Women’s Health Research Institute, Wyeth-Ayerst Research (S.G.L., J.M.C., R.C.W.), Radnor, Pennsylvania 19087; and Cardiovascular Research, Wyeth-Ayerst Research (M.-L.M.), Princeton, New Jersey 08852

Address all correspondence and requests for reprints to: Scott G. Lundeen, Ph.D., Women’s Health Research Institute, Wyeth-Ayerst Laboratories, 145 King of Prussia Road, Radnor, Pennsylvania 19087. E-mail address: lundees{at}war.wyeth.com

Estrogens protect against cardiovascular disease in women through effects on the vascular wall and liver. Here we further characterize the rat as a model for the evaluation of estrogenic effects on plasma lipid levels vs. uterine wet weight. In adult ovariectomized female rats treated for 4 days sc, 17-ethinyl estradiol (EE) was the most potent agent to lower plasma total and high density lipoprotein cholesterol levels, followed by 17ß-estradiol and 17-estradiol. However, 17-estradiol had the greatest separation of uterotropic vs. cholesterol-lowering effects. EE had the same lipid-lowering potency whether administered sc or orally to adult rats. It had no effect on cholesterol levels in immature rats, even though the uterotropic response was dramatic. Testosterone propionate, dexamethasone, and progesterone did not significantly lower cholesterol levels. The antiestrogens tamoxifen and raloxifene lowered cholesterol levels, but with less efficacy and potency than the estrogens. ICI 182780 had no effect on cholesterol levels. When coadministered with EE, ICI 182780 inhibited the cholesterol-lowering and uterotropic activities of EE, suggesting that the estrogen receptor pathway is involved. In conclusion, although the information from the rat is limited as a model of the low density lipoprotein-lowering effects of estrogens in humans, it can be used to study the effects and mechanism of action of estrogen and antiestrogens on plasma cholesterol levels.

This article has been cited by other articles:

				Y. Kharode, P. V. N. Bodine, C. P. Miller, C. R. Lyttle, and B. S. Komm The Pairing of a Selective Estrogen Receptor Modulator, Bazedoxifene, with Conjugated Estrogens as a New Paradigm for the Treatment of Menopausal Symptoms and Osteoporosis Prevention Endocrinology, December 1, 2008; 149(12): 6084 - 6091. [Abstract] [Full Text] [PDF]

				P. D. Alfinito, X. Chen, J. Atherton, S. Cosmi, and D. C. Deecher ICI 182,780 Penetrates Brain and Hypothalamic Tissue and Has Functional Effects in the Brain after Systemic Dosing Endocrinology, October 1, 2008; 149(10): 5219 - 5226. [Abstract] [Full Text] [PDF]

				N. J. MacLusky, V. N. Luine, T. Hajszan, and C. Leranth The 17{alpha} and 17{beta} Isomers of Estradiol Both Induce Rapid Spine Synapse Formation in the CA1 Hippocampal Subfield of Ovariectomized Female Rats Endocrinology, January 1, 2005; 146(1): 287 - 293. [Abstract] [Full Text] [PDF]

				P. E. Goss, S. Qi, A. M. Cheung, H. Hu, M. Mendes, and K. P. H. Pritzker Effects of the Steroidal Aromatase Inhibitor Exemestane and the Nonsteroidal Aromatase Inhibitor Letrozole on Bone and Lipid Metabolism in Ovariectomized Rats Clin. Cancer Res., September 1, 2004; 10(17): 5717 - 5723. [Abstract] [Full Text] [PDF]

				J.-x. Zhang, D. C. Labaree, G. Mor, and R. B. Hochberg Estrogen to Antiestrogen with a Single Methylene Group Resulting in an Unusual Steroidal Selective Estrogen Receptor Modulator J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3527 - 3535. [Abstract] [Full Text] [PDF]

				J. A. Kramer, J. LeDeaux, D. Butteiger, T. Young, C. Crankshaw, H. Harlow, L. Kier, and B. G. Bhat Transcription Profiling in Rat Liver in Response to Dietary Docosahexaenoic Acid Implicates Stearoyl-Coenzyme A Desaturase as a Nutritional Target for Lipid Lowering J. Nutr., January 1, 2003; 133(1): 57 - 66. [Abstract] [Full Text] [PDF]

				H. A. Harris, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Characterization of the Biological Roles of the Estrogen Receptors, ER{alpha} and ER{beta}, in Estrogen Target Tissues in Vivo through the Use of an ER{alpha}-Selective Ligand Endocrinology, November 1, 2002; 143(11): 4172 - 4177. [Abstract] [Full Text] [PDF]

				H. Y. Chan, X. Yao, S. Y. Tsang, J.-P. Bourreau, F. L. Chan, and Y. Huang Isoproterenol amplifies 17{beta}-estradiol-mediated vasorelaxation: role of endothelium/nitric oxide and cyclic AMP Cardiovasc Res, February 15, 2002; 53(3): 627 - 633. [Abstract] [Full Text] [PDF]

				J. M. Fitts, R. M. Klein, and C. A. Powers Estrogen and Tamoxifen Interplay with T3 in Male Rats: Pharmacologically Distinct Classes of Estrogen Responses Affecting Growth, Bone, and Lipid Metabolism, and Their Relation to Serum GH and IGF-I Endocrinology, October 1, 2001; 142(10): 4223 - 4235. [Abstract] [Full Text] [PDF]

				A. D. Papaconstantinou, T. H. Umbreit, B. R. Fisher, P. L. Goering, N. T. Lappas, and K. M. Brown Bisphenol A-Induced Increase in Uterine Weight and Alterations in Uterine Morphology in Ovariectomized B6C3F1 Mice: Role of the Estrogen Receptor Toxicol. Sci., August 1, 2000; 56(2): 332 - 339. [Abstract] [Full Text] [PDF]

				J. F. Couse and K. S. Korach Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us? Endocr. Rev., June 1, 1999; 20(3): 358 - 417. [Abstract] [Full Text]

				M. A. Pelleymounter, M. B. Baker, and M. McCaleb Does estradiol mediate leptin's effects on adiposity and body weight? Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E955 - E963. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit and D. M. Shoback Clinical Effects of Raloxifene Hydrochloride in Women Ann Intern Med, March 2, 1999; 130(5): 431 - 439. [Abstract] [Full Text] [PDF]

				J. D. Sibonga, H. Dobnig, R. M. Harden, and R. T. Turner Effect of the High-Affinity Estrogen Receptor Ligand ICI 182,780 on the Rat Tibia Endocrinology, September 1, 1998; 139(9): 3736 - 3742. [Abstract] [Full Text] [PDF]

				S. Luo, A. Sourla, C. Labrie, A. Belanger, and F. Labrie Combined Effects of Dehydroepiandrosterone and EM-800 on Bone Mass, Serum Lipids, and the Development of Dimethylbenz(A)Anthracene-Induced Mammary Carcinoma in the Rat Endocrinology, October 1, 1997; 138(10): 4435 - 4444. [Abstract] [Full Text] [PDF]