Summary
In the mouse, the anabolic effect of estrogen on the uterus and its stimulatory effect on endosteal bone formation are well documented. When these observations are coupled with the recent description of uterine-derived bone cell mitogens, it raises the possibility that uterine hypertrophy in response to estrogen might lead to the production and release of factors that participate in the skeleton's anabolic response to estrogen. To determine if the stimulatory effects of estrogen on endosteal bone formation and uterine tissue in the mouse are related, we have studied this specific skeletal response to ovariectomy (OVX) and ovariohysterectomy (OHTX), and to two levels of 17β-estradiol (17β-E2). To assess treatment effects, 48 Swiss-webster mice were assigned to six groups: OHTX/oil vehicle, OVX/oil vehicle, OHTX/150 μg 17β-E2, OHTX/300 μg 17β-E2, OVX/150 μg 17β-E2, and OVX/300 μg 17β-E2. Animals were treated once per week with vehicle or the respective 17β-E2 dose. To quantitate bone formation, fluorochrome labels were administered at the beginning and end of the experimental period. At the conclusion of the 5-week study, tibiae were processed undecalcified for embedding in methyl methacrylate plastic. Cross-sectional areal properties and bone formation rates were quantitated from 30 μm mid-diaphyseal sections using a Bioquant Bone Morphometry system. Compared with the vehicle-treated OVX and OHTX mice, 150 μg of 17β-E2 administered once per week significantly increased cortical bone areas (P<0.05) but cortical bone widths and the ratio of cortical bone area to total bone area was increased only in estrogen-treated OVX mice (P<0.01). The attenuation of bone formation in the OHTX mice was even more apparent in animals treated with 300 μg 17β-E2. Endosteal mineral apposition and bone formation, cortical bone widths, and cortical bone ratios were all significantly reduced in OHTX mice compared with OVX animals treated with the same 17β-E2 dose. Indeed, the 17β-E2-induced cortical bone increases in the OVX animals were reduced 50% by OHTX. These results suggest that the anabolic effects of high-dose 17β-E2 on endosteal bone formation in the mouse are modulated by estrogen's uterotrophic activity, and are therefore consistent with the hypothesis that the uterus may produce and release factors with the capacity to stimulate bone formation.
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Bain, S.D., Bailey, M.C. & Edwards, M.W. The anabolic effect of estrogen on endosteal bone formation in the mouse is attenuated by ovariohysterectomy: A role for the uterus in the skeletal response to estrogen?. Calcif Tissue Int 51, 223–228 (1992). https://doi.org/10.1007/BF00334551
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DOI: https://doi.org/10.1007/BF00334551