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?
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 17 beta-estradiol (17 beta-E2). To assess treatment effects, 48 Swiss-webster mice were assigned to six groups: OHTX/oil vehicle, OVX/oil vehicle, OHTX/150 micrograms 17 beta-E2, OHTX/300 micrograms 17 beta-E2, OVX/150 micrograms 17 beta-E2, and OVX/300 micrograms 17 beta-E2. Animals were treated once per week with vehicle or the respective 17 beta-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 microns mid-diaphyseal sections using a Bioquant Bone Morphometry system. Compared with the vehicle-treated OVX and OHTX mice, 150 micrograms of 17 beta-E2 administered once per week significantly increased cortical bone areas (P less than 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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Bain
S D
SD
Osteoporosis and Hard Tissue Repair Laboratory, ZymoGenetics, Inc., Seattle, Washington 98105.
Bailey
M C
MC
Edwards
M W
MW
D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006984:Hypertrophy; D007044:Hysterectomy; D051379:Mice; D008856:Microscopy, Fluorescence; D010052:Ovariectomy; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D004967:Estrogens