© 1996 American Heart Association, Inc.
Articles |
Oral Estrogen Replacement Therapy in Postmenopausal Women Selectively Raises Levels and Production Rates of Lipoprotein A-I and Lowers Hepatic Lipase Activity Without Lowering the Fractional Catabolic Rate
From the Department of Internal Medicine, Bowman Gray School of Medicine, Winston-Salem, NC.
Correspondence to Eliot A. Brinton, MD, Department of Internal Medicine, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1047. E-mail ebrinton@bgsm.edu.
Abstract To characterize the apolipoprotein (apo) subfraction specificity of the increase in high density lipoprotein (HDL) levels that is induced by oral estrogen and to explore the metabolic mechanisms thereof, six healthy, postmenopausal women were studied during each of two 5-week periods of a low-fat diet with and without ethinyl estradiol 0.05 mg/d. With estrogen, HDL cholesterol levels increased 36% (mean±SD, 47±15 versus 63±18 mg/dL, basal versus estrogen periods, respectively; P=.004), plasma levels of apo A-I increased by 27% (147±24 versus 186±34 mg/dL; P=.003), and apo A-II levels increased 17% (39±5 versus 46±4 mg/dL; P=.0003). Apo A-I mass in particles that contained apo A-I but no apo A-II (ie, Lp A-I) increased 66% (43±13 versus 71±17 mg/dL; P=.002) while the sum of apo A-I and apo A-II mass in particles with both apo A-I and apo A-II (ie, Lp A-I/A-II) showed only a nonsignificant 14% increase (144±23 versus 163±29 mg/dL; P=.12). In radioiodinated-protein turnover studies the production rate (PR) of each species changed in proportion to the change in its plasma concentration: Lp A-I PR increased 76% (4.7±1.8 versus 8.2±2.5 mg·kg-1·day-1; P=.001) while Lp A-I/A-II PR showed only a nonsignificant increase of 22% (14.1±1.8 versus 17.2±5.4 mg·kg-1·day-1; P=.2). Hepatic lipase (HL) activity in postheparin plasma decreased 66% with estrogen (10.4±4.3 versus 3.5±0.8 µmol·mL-1·h-1; P=.005) while lipoprotein lipase activity was unchanged (7.1±1.6 versus 7.6±1.6 µmol·mL-1·h-1; P>.2). Despite the large decrease in HL activity, the fractional catabolic rate of Lp A-I did not decrease (0.241±0.048 versus 0.258±0.066 pool/d; P=.2), nor was that of Lp A-I/A-II lessened (0.221±0.030 versus 0.233±0.053 pool/d; P>.2). Thus, oral estrogen replacement therapy has a novel and potentially antiatherogenic effect: a large and selective increase in Lp A-I levels. The metabolic mechanism of the estrogen-induced increase in Lp A-I concentration appears to be the increase in its PR. Although the ability of estrogen to suppress HL activity has been confirmed, surprisingly this decrease was not accompanied by any decrease in the fractional catabolic rate of Lp A-I or Lp A-I/A-II. This suggests that HL may not play a major role in regulating HDL protein catabolism during suppression of HL by estrogen.
Key Words: HDL • turnover kinetics • ethinyl estradiol • postmenopausal women • hepatic lipase
This article has been cited by other articles:
 |
|
 |
|
  M. Walter Interrelationships Among HDL Metabolism, Aging, and Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2009; 29(9): 1244 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kolovou, D. Damaskos, K. Anagnostopoulou, and D. V. Cokkinos Apolipoprotein E Gene Polymorphism and Gender Ann. Clin. Lab. Sci., January 1, 2009; 39(2): 120 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L Hall, K. Vafeiadou, J. Hallund, S. Bugel, M. Reimann, C. Koebnick, H-J F. Zunft, M. Ferrari, F. Branca, T. Dadd, et al. Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production Am. J. Clinical Nutrition, March 1, 2006; 83(3): 592 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lamon-Fava, B. Postfai, M. Diffenderfer, C. DeLuca, J. O'Connor Jr, F. K. Welty, G. G. Dolnikowski, P. H. R. Barrett, and E. J. Schaefer Role of the Estrogen and Progestin in Hormonal Replacement Therapy on Apolipoprotein A-I Kinetics in Postmenopausal Women Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 385 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lamon-Fava, J. B. Barnett, M. N. Woods, C. McCormack, J. R. McNamara, E. J. Schaefer, C. Longcope, B. Rosner, and S. L. Gorbach Differences in Serum Sex Hormone and Plasma Lipid Levels in Caucasian and African-American Premenopausal Women J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4516 - 4520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Fan, P. Dastidar, H. Jokela, R. Punnonen, and T. Lehtimaki Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3786 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gotto Jr and E. A. Brinton Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: A working group report and update J. Am. Coll. Cardiol., March 3, 2004; 43(5): 717 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Barnett, M. N. Woods, S. Lamon-Fava, E. J. Schaefer, J. R. McNamara, D. Spiegelman, E. Hertzmark, B. Goldin, C. Longcope, and S. L. Gorbach Plasma Lipid and Lipoprotein Levels during the Follicular and Luteal Phases of the Menstrual Cycle J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 776 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lamon-Fava and D. Micherone Regulation of apoA-I gene expression: mechanism of action of estrogen and genistein J. Lipid Res., January 1, 2004; 45(1): 106 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Cheung, S. D. Sibley, J. P. Palmer, J. F. Oram, and J. D. Brunzell Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I,A-II) J. Lipid Res., August 1, 2003; 44(8): 1552 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Deeb, A. Zambon, M. C. Carr, A. F. Ayyobi, and J. D. Brunzell Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet J. Lipid Res., July 1, 2003; 44(7): 1279 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Brown, M. C. Cheung, A. C. Lee, X.-Q. Zhao, and A. Chait Antioxidant Vitamins and Lipid Therapy: End of a Long Romance? Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1535 - 1546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington, T. D. Howard, G. A. Hawkins, D. M. Reboussin, J. Xu, S. L. Zheng, K. B. Brosnihan, D. A. Meyers, and E. R. Bleecker Estrogen-Receptor Polymorphisms and Effects of Estrogen Replacement on High-Density Lipoprotein Cholesterol in Women with Coronary Disease N. Engl. J. Med., March 28, 2002; 346(13): 967 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Jones, R. J. Schmidt, R. T. Pickard, P. S. Foxworthy, and P. I. Eacho Estrogen receptor-mediated repression of human hepatic lipase gene transcription J. Lipid Res., March 1, 2002; 43(3): 383 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S Mikkola and T. B Clarkson Estrogen replacement therapy, atherosclerosis, and vascular function Cardiovasc Res, February 15, 2002; 53(3): 605 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Saucan and E. A. Brinton Lp A-I and Niacin: New Views of an Antiatherogenic Duo Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1707 - 1709. [Full Text] [PDF]
|
|
|
|
|
|
T. Sakai, V. S. Kamanna, and M. L. Kashyap Niacin, but Not Gemfibrozil, Selectively Increases LP-AI, a Cardioprotective Subfraction of HDL, in Patients With Low HDL Cholesterol Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1783 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Velez-Carrasco, A. H. Lichtenstein, Z. Li, G. G. Dolnikowski, S. Lamon-Fava, F. K. Welty, and E. J. Schaefer Apolipoprotein A-I and A-II Kinetic Parameters as Assessed by Endogenous Labeling With [2H3]Leucine in Middle-Aged and Elderly Men and Women Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 801 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Nanjee and E. A. Brinton Very Small Apolipoprotein A-I-containing Particles from Human Plasma: Isolation and Quantification by High-Performance Size-Exclusion Chromatography Clin. Chem., February 1, 2000; 46(2): 207 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lamon-Fava, J. M. Ordovas, and E. J. Schaefer Estrogen Increases Apolipoprotein (Apo) A-I Secretion in Hep G2 Cells by Modulating Transcription of the Apo A-I Gene Promoter Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2960 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Weng, N. A. Brandenburg, S. Zhong, J. Halkias, L. Wu, X.-c. Jiang, A. Tall, and J. L. Breslow ApoA-II maintains HDL levels in part by inhibition of hepatic lipase: studies in apoA-II and hepatic lipase double knockout mice J. Lipid Res., June 1, 1999; 40(6): 1064 - 1070. [Abstract] [Full Text]
|
|
|
|
|
|
F.-Y. Jin, V. S. Kamanna, and M. L. Kashyap Estradiol Stimulates Apolipoprotein A-I– but Not A-II–Containing Particle Synthesis and Secretion by Stimulating mRNA Transcription Rate in Hep G2 Cells Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 999 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Harnish, M. J. Evans, M. S. Scicchitano, R. A. Bhat, and S. K. Karathanasis Estrogen Regulation of the Apolipoprotein AI Gene Promoter through Transcription Cofactor Sharing J. Biol. Chem., April 10, 1998; 273(15): 9270 - 9278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sudhir, T. M. Chou, K. Chatterjee, E. P. Smith, T. C. Williams, J. P. Kane, M. J. Malloy, K. S. Korach, and G. M. Rubanyi Premature Coronary Artery Disease Associated With a Disruptive Mutation in the Estrogen Receptor Gene in a Man Circulation, November 18, 1997; 96(10): 3774 - 3777. [Abstract] [Full Text]
|
|