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Important Issues. Roles of ERa and ERb Distinct Functions of PR-A and PR-B Selective Ligands (SERMs and SPRMs) Coregulators Interrelationships Between Estrogen and Progestin Hormone-Receptor Pathways Tissue Selectivity in Estrogen and Progestin Actions. . Target Tissues in Females
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1. OVERVIEWBiology of Estrogen & Progesterone Receptors
3. Target Tissues in Females & Males
4. Estrogen Receptor in Breast Cancer
5. New York Times, April 7, 1998, p. A1
6. Tissue Selectivity
9. Human Estrogen Receptors a and b Human Estrogen Receptors ? and ?
Human Estrogen Receptors ? and ?
10. Exquisite Precision in Receptor Regulation
11. Ligands for Estrogen Receptors
12. SERM Action
13. Structures of Diethylstilbestrol-ERa LBD and Hydroxytamoxifen-ERa LBD
14. PPT, an ERa Specific Ligand, Prevents Ovariectomy-Induced Loss of Bone Mineral Density
15. PPT, an ERa Specific Ligand, Prevents Hot Flush in a Rat Model
17. Estrogen Effects on Cell Cytoarchitecture
19. Estrogen Receptor Beta
20. ERb in Human Breast
21. Of 37 genes stim by E2 - -
A,B,C -- expected patterns
D,E,F -- unusual patternsOf 37 genes stim by E2 - -
A,B,C -- expected patterns
D,E,F -- unusual patterns
22. Comparative Patterns of Gene Stimulation by Estradiol and SERMs (MCF-7 Cells) [n = 33] TOT , considered the most estrogen-like SERMTOT , considered the most estrogen-like SERM
23. SERM Antagonism of Estradiol Stimulation (MCF-7 Cells) [n = 35] Of 37 genes stim by E2 - -
A,B,C -- expected patterns
D,E,F -- unusual patternsOf 37 genes stim by E2 - -
A,B,C -- expected patterns
D,E,F -- unusual patterns
24. Progesterone Receptor
25. Ligands for Progesterone Receptor
26. Human Progesterone Receptor: A and B Forms
27. Human Progesterone Receptor Isoforms A and B
28. Interrelationships Between Estrogen and Progestin Receptor Signaling Pathways
29. Women’s Health Initiative (WHI) Clinical Trial
30. Would outcome be different if:
32. Take-Home Messages
34. Questions that Remain