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1. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004; 291: 1701-12. [PMID: 15082697] 2. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002; 288: 321-33. [PMID: 12117397] 3. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998; 280: 1569-75. [PMID: 9820257] 4. Oldendick R, Coker AL, Wieland D, Raymond JI, Probst JC, Schell BJ, et al. Population-based survey of complementary and alternative medicine usage, patient satisfaction, and physician involvement. South Carolina Complementary Medicine Program Baseline Research Team. South Med J. 2000; 93: 375-81. [PMID: 10798505] 5. Newton KM, Buist DS, Keenan NL, Anderson LA, LaCroix AZ. Use of alternative therapies for menopause symptoms: results of a population-based survey. Obstet Gynecol. 2002; 100: 18-25. [PMID: 12100799] 6. Keenan NL, Mark S, Fugh-Berman A, Browne D, Kaczmarczyk J, Hunter C. Severity of menopausal symptoms and use of both conventional and complementary alternative therapies. Menopause. 2003; 10: 507-15. [PMID: 14627858] 7. Newton KM, Reed SD, Grothaus L, Ehrlich K, Guiltinan J, Ludman E, et al. The Herbal Alternatives for Menopause HALT ; Study: background and study design. Maturitas. 2005; 52: 134-46. [PMID: 16186076] 8. Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003; 289: 2663-72. [PMID: 12771113] 9. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive im878 19 December 2006 Annals of Internal Medicine Volume 145 Number 12.
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Sion Figure 6C ; , which was mirrored by a decrease in cellular MMP-9 protein Figure 6D ; . To further determine the mechanisms responsible for inhibition of MMP-9 expression by PGE2, selective pharmacological agonists and or antagonists of EP receptors were used to treat peritoneal macrophages. Treatment with EP2 agonist butaprost, 10 mol L ; exerted a similar effect as those treated with PGE2 whereas treatment with EP3 agonist sulprostone, 10 mol L ; failed to inhibit MMP-9 expression Figure 7A ; . Co-treatment with PGE1OH EP2 EP4 agonist, 10 mol L ; and AH6809 EP1 EP2 antagonist, 80 mol L ; also inhibited MMP-9 expression indicating that effect of PGE2 may also be mediated via EP4 receptor Figure 7A ; . To test whether the lack of effect of EP3 agonist was due to lack of EP3 receptor expression, RT-PCR was used to evaluate the presence or absence of different EP receptor isoforms in peritoneal macrophages. The result demonstrated that three EP receptor isoforms, EP2, EP3, and EP4 were expressed in macrophages whereas EP1 receptor was undetectable Figure 7B ; . The downstream signaling of EP2 EP4 was mediated via protein kinase A PKA ; pathway. Thus, a PKA inhibitor, H89 was used to block actions of PGE2. Pretreatment with H89 10 mol L ; reversed PGE2-mediated inhibition of MMP-9 expression Figure 7C ; and activity Figure 7D ; . Concordantly, H89 also relieved butaprost-suppressed MMP-9 protein expression Figure 7D and altace.
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