دورية
Estrogen Receptor (ER)-α, but Not ER-β, Mediates Regulation of the Insulin-like Growth Factor I Gene by Antiestrogens*
| العنوان: | Estrogen Receptor (ER)-α, but Not ER-β, Mediates Regulation of the Insulin-like Growth Factor I Gene by Antiestrogens* |
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| المؤلفون: | Fournier, Brigitte, Gutzwiller, Sabine, Dittmar, Tanja, Matthias, Gabriele, Steenbergh, Paul, Matthias, Patrick |
| المصدر: | Journal of Biological Chemistry; September 2001, Vol. 276 Issue: 38 p35444-35449, 6p |
| مستخلص: | The importance of insulin-like growth factor I (IGF-I) on maintenance of skeletal integrity has been widely recognized. Although osteoblasts secrete some IGF-I, the liver is the primary endocrine source for IGF-I. We have studied the regulation of the human IGF-I promoter in the hepatocyte cell line Hep3B, and we have shown that the IGF-I promoter, when co-transfected in Hep3B cells together with an estrogen receptor (ER)-α expression vector, was transcriptionally regulated by raloxifene or raloxifene-like molecules but not by 17β-estradiol and 4(OH)-tamoxifen. The induction mediated by raloxifene is antagonized by 17β-estradiol and mediated selectively by ER-α, but not by ER-β. Transfer of IGF-I promoter sequences from −733 to −65 or from −375 to −65 to a minimal Fos promoter resulted in a comparable responsiveness to raloxifene. This region contains two CAAT/enhancer-binding protein sites and an activator protein 1 site, both of which have been shown to be involved in estrogen receptor-mediated transactivation. When the CAAT/enhancer-binding protein sites were mutated in a construct bearing the sequence from −375 to −65 in front of the minimal Fos promoter, raloxifene induction was reduced, whereas mutation of the other elements did not affect induction. In addition, using chimeric proteins, we delineated the domains of ER-α that confer to ER-α transactivation abilities on the IGF-I promoter that are not exhibited by ER-β. These data shed new light on the mechanism of action of antiestrogens and might help explain, at least in part, the bone-protective effects observed for some antiestrogens in ovariectomized animals. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00219258 1083351X |
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| DOI: | 10.1074/jbc.M105418200 |