The discovery of a second estrogen receptor, ER β, in 1996 introduced a new paradigm in our understanding of estrogen action. ER α predominates in the uterus and mammary gland, whereas ER β has significant roles in the central nervous, cardiovascular, and immune systems, urogenital tract, bone, kidney, and lung. ER β appears to be the only form expressed in the embryonal central nervous system. Photoestrogens may be good candidates for physiologic ligands of ER β. Coactivator proteins play critical roles in regulating estrogen. Female ER β-deleted mice (βERKO) develop follicular arrest and anovulation.
1. Kuiper GGJM, Emmark E, Pelto-Huikko M, et al. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA1996;93:5925-5930.
2.
2. Enmark E, Pelto-Huikko M, Grandien M, et al. Human estrogen β-gene structure, chromosomal localization, expression pattern. J Clin Endocrinol Metab1997;82:4258-4265.
3.
3. Kuiper GGJM, Shughrue PJ, Pelto-Huikko M, et al. The estrogen receptor β subtype: A novel mediator of estrogen action in neuroendocrine systems. Frontiers in Neuroendocrinol1998;19;253-286.
4.
4. Kuiper GGJM, Carlquist M, Gustafsson J.-Å. Estrogen is a male and female hormone. Science & Medicine1998;5:36-45.
5.
5. Gustafsson J.-Å. Raloxifene: Magic bullet for heart and bone?Nature Medicine1998;4:152-152.
6.
6. Kuiper GGJM, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinol1997;3:863-870.
7.
7. Lindner V, Kim SK, Karas RH, et al. Increased expression of estrogen receptor-β mRNA in male blood vessels after vascular injury. Circ Res1998;83:224-229.
8.
8. Byers M, Kuiper GGJM, Gustafsson J.-Å., et al. Estrogen receptor-β mRNA expression in rat ovary: Down-regulation by gonadotropins. Mol Endocrinol1997;11:172-182.
9.
9. Paech K, Webb P, Kuiper GGJM, et al. Differential transactivation properties of the estrogen receptor isotypes (α,β): Estrogen-like effects with antiestrogens and antiestrogen effects with estrogen. Science1997;277:1508-1510.
10.
10. Montano MM, Jaiswal AK, Katzenellenbogen BS. Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-α and estrogen receptor-β. J Biol Chem1998;273:25443-25449.
11.
11. Prins FS, Marmer M, Woodham C, et al. Estrogen receptor beta mRNA ontogeny in the rat prostate and effects of neonatal estrogen exposure on the expression pattern. Endocrinol1998;139:874-883.
12.
12. Lemmen JG, Broekhof JLM, Kuiper GGJM, et al. Expression of estrogen receptor alpha and beta during mouse embryogenesis. Mech Dev1999;81:163-167.
13.
13. Johansson L, Thomsen JS, Damdimopoulos AE, et al. The orphan nuclear receptor SHP inhibits agonist-dependent transcriptional activity of estrogen receptors ERα and ER β. J Biol Chem1999;247:345-353.
14.
14. Seol W, Hanstein B, Brown M, Moore DD. Inhibition of estrogen receptor action by the orphan receptor SHP (Short Heterodimer Partner). Mol Endocrinol1998;12:1551-1557.
15.
15. Krege JH, Hodgin JB, Couse JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor β. Proc Natl Acad Sci USA1998;95:15677-15682.
