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Titolo:
Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: Role of locally produced growth factors
Autore:
Bord, S; Beavan, S; Ireland, D; Horner, A; Compston, JE;
Indirizzi:
Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 2QQ, England Univ Cambridge Cambridge England CB2 2QQ Med, Cambridge CB2 2QQ, England
Titolo Testata:
BONE
fascicolo: 3, volume: 29, anno: 2001,
pagine: 216 - 222
SICI:
8756-3282(200109)29:3<216:MBWHET>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
OSTEOBLAST-LIKE CELLS; FACTOR-BETA; LONG-TERM; REPLACEMENT THERAPY; BONE-FORMATION; MESSENGER-RNA; FACTOR-I; EXPRESSION; ACID; DIFFERENTIATION;
Keywords:
estrogen; bone; transforming growth factor-beta (TGF-beta); platelet derived growth factor (PDGF); megakaryocytes; tartrate-resistant acid phosphatase (TRAP);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Bord, S Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Box 157, Cambridge CB2 2QQ, England Univ Cambridge Box 157 Cambridge England CB2 2QQ CB2 2QQ, England
Citazione:
S. Bord et al., "Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: Role of locally produced growth factors", BONE, 29(3), 2001, pp. 216-222

Abstract

Conventional hormone replacement therapy acts primarily by preserving bone, but cannot restore lost bone in women with established osteoporosis. Studies in rodents have shown that high doses of estrogens have anabolic skeletal effects, and recent observations in a group of women treated long term with high doses of estrogen indicated that similar effects occur in humans. This study examines the hypothesis that locally produced growth factors, including transforming growth factor-beta (TGF-beta) and platelet-derived growth factors (PDGFs), are involved in mediating the anabolic effects of high-dose estrogen. Transiliac-crest bone biopsies were taken from ten women, aged 52-67 years (mean 58 years), who had been treated with high-dose estrogen for 15 years. Control samples were obtained from four age-matched postmenopausal women not receiving estrogen therapy. TGF-betas and PDGFs were analyzed for mRNA and protein expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed both TGF-beta1 and -beta2 mRNA, expressed as a ratio to GAPDH, were increased in the estrogen-treated group with an eightfold increase for TGF-beta1 (0.258 +/- 0.246 [mean +/- SD] vs. 0.032 +/- 0.053 in the control group, p = 0.02) and a twofold increase for TGF-beta2 (p = n.s.). TGF-beta3 analysis showed onlynegligible amounts in both groups. Protein expression levels for TGF-beta1, -beta2, -beta RI and -RII were higher in the estrogen-treated group than in controls, the most marked effects being seen for TGF-beta1. PDGF-A protein expression was also significantly higher in osteoblasts and osteocytes in women treated with estrogen, whereas PDGF-B showed only modest differences. The percentage of bone surface occupied by osteoclasts, as determined bytartrate-resistant acid phosphatase (TRAP) staining, was significantly reduced in the estrogen-treated group (p = 0.001). These results demonstrate that high-dose estrogen therapy is associated with increased TGF-beta, TGF-betaR, and PDGF synthesis and decreased osteoclast activity, consistent withthe hypothesis that these growth factors may mediate the actions of estrogen in bone. (Bone 29:216-222; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:15:59