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Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor α and β Pathways *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 275, Issue: 28, Page: 21372-21379
2000
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Article Description

Although it is well established that estrogen deficiency causes osteoporosis among the postmenopausal women, the involvement of estrogen receptor (ER) in its pathogenesis still remains uncertain. In the present study, we have generated rats harboring a dominant negative ERα, which inhibits the actions of not only ERα but also recently identified ERβ. Contrary to our expectation, the bone mineral density (BMD) of the resulting transgenic female rats was maintained at the same level with that of the wild-type littermates when sham-operated. In addition, ovariectomy-induced bone loss was observed almost equally in both groups. Strikingly, however, the BMD of the transgenic female rats, after ovariectomized, remained decreased even if 17β-estradiol (E 2 ) was administrated, whereas, in contrast, the decrease of littermate BMD was completely prevented by E 2. Moreover, bone histomorphometrical analysis of ovariectomized transgenic rats revealed that the higher rates of bone turnover still remained after treatment with E 2. These results demonstrate that the prevention from the ovariectomy-induced bone loss by estrogen is mediated by ER pathways and that the maintenance of BMD before ovariectomy might be compensated by other mechanisms distinct from ERα and ERβ pathways.

Bibliographic Details

Sumito Ogawa; Masayo Fujita; Yasunori Ishii; Hiroshi Tsurukami; Masami Hirabayashi; Kazuhiro Ikeda; Akira Orimo; Takayuki Hosoi; Masatsugu Ueda; Toshitaka Nakamura; Yasuyoshi Ouchi; Masami Muramatsu; Satoshi Inoue

Elsevier BV

Biochemistry, Genetics and Molecular Biology

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