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| Estrogen and raloxifene stimulate transforming growth factor-beta 3 gene expression in rat bone: A potential mechanism for estrogen- or raloxifene-mediated bone maintenance |
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| Author(s): Yang NN, Bryant HU, Hardikar S, Sato M, Galvin RJS, Glasebrook AL, Termine JD |
| Source: ENDOCRINOLOGY Volume: 137 Issue: 5 Pages: 2075-2084 Published: MAY 1996 |
| Times Cited: 71 References: 54 |
| Abstract: Estrogen or raloxifene (LY156758) prevent estrogen deficiency-induced bone loss in animals and humans. We demonstrated in the rat that a 22% reduction in bone mineral density generated by ovariectomy was associated with a 2-fold reduction of transforming growth factor-beta 3 (TGF beta 3) messenger RNA expression in the femur. Administration of 17 beta-estradiol or raloxifene to ovariectomized rats restored both bone mineral density and TGF beta 3 messenger RNA expression in the femur to levels measured in intact animals. In transient transfection assays, the promoter sequence from -38 to +110 of the human TGF beta 3 gene, which contains no palindromic estrogen response element, was sufficient to mediate 17 beta-estradiol or raloxifene induced-reporter gene expression in presence of the estrogen receptor. Raloxifene activated TGF beta 3 promoter as a full agonist at nanomolar concentrations. In the same cellular system, raloxifene inhibited the estrogen response element-containing vitellogenin promoter expression as a pure estrogen antagonist. In two well characterized osteoclast differentiation models, TGF beta 3 significantly inhibited the differentiation and bone-resorptive activities of murine and avian osteoclasts. These findings suggest that regulation of TGF beta 3 gene expression by raloxifene or estrogen in bone may be an important target to mediate bone maintenance. |
| Document Type: Article |
| Language: English |
| Reprint Address: Yang, NN (reprint author), ELI LILLY & CO, LILLY RES LAB, LILLY CORP CTR, DC 0444, INDIANAPOLIS, IN 46285 USA |
| Publisher: ENDOCRINE SOC, 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: UG636 |
| ISSN: 0013-7227 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |