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Publication : Estrogen receptor-alpha dependency of estrogen's stimulatory action on cancellous bone formation in male mice.

First Author  McDougall KE Year  2003
Journal  Endocrinology Volume  144
Issue  5 Pages  1994-9
PubMed ID  12697707 Mgi Jnum  J:115709
Mgi Id  MGI:3692096 Doi  10.1210/en.2002-0074
Citation  McDougall KE, et al. (2003) Estrogen receptor-alpha dependency of estrogen's stimulatory action on cancellous bone formation in male mice. Endocrinology 144(5):1994-9
abstractText  We examined whether estrogen receptor (ER)alpha is required for estrogen to stimulate cancellous bone formation in long bones of male mice. 17 beta-Estradiol (E(2)) was administered to ER alpha(-/-) male mice or wild-type (WT) littermate controls at 40, 400, or 4000 microg/kg by daily sc injection for 28 d and histomorphometric analysis performed at the distal femoral metaphysis. In WT mice, treatment with E(2) (40 microg/kg per d) increased the proportion of cancellous bone surfaces undergoing mineralization and stimulated mineral apposition rate. In addition, higher doses of E(2) induced the formation of new cancellous bone formation surfaces in WT mice. In contrast, E(2) had little effect on any of these parameters in ER alpha(-/-) mice. Immunohistochemistry was subsequently performed using an ER alpha-specific C-terminal polyclonal antibody. In WT mice, ER alpha was expressed both by cancellous osteoblasts and a significant proportion of mononuclear bone marrow cells. Immunoreactivity was also observed in cancellous osteoblasts of ER alpha(-/-) mice, resulting from expression of the activation function-1-deficient 46-kDa ER alpha isoform previously reported to be expressed in normal osteoblasts and bones of ER alpha(-/-) mice. Taken together, our results suggest that estrogen stimulates bone formation in mouse long bones via a mechanism that requires the presence of full-length ER alpha possessing activation function-1.
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