Effects of estrogen and tamoxifen on serum osteocalcin levels in ovariectomized rats.
Serum osteocalcin levels were measured in ovariectomized rats treated for 35 days with either estrogens (ethynylestradiol administered orally or 17 beta-estradiol administered by subcutaneous injection) or the antiestrogenic compound tamoxifen (administered both orally and subcutaneously). Tamoxifen is a non-steroidal compound that has mixed agonist/antagonist actions in several biological models, but is commonly referred to as an 'antiestrogen'. Administration of tamoxifen, like estrogen, caused a reduction in the increases in animal body weight and femur length during the test period, and greater bone density in the distal femur metaphysis compared to ovariectomized control animals. Both the estrogens and tamoxifen caused a dose-dependent decrease in serum osteocalcin as compared to the levels in the serum of ovariectomized control rats; however, tamoxifen displayed both reduced potency and efficacy compared to estrogens. Serum osteocalcin levels declined in a linear fashion throughout the estrogen dose range, and at the highest doses tested (400 micrograms/kg/d ethynylestradiol; 100 micrograms/kg/d 17 beta-estradiol), osteocalcin levels were reduced by 45-50% compared to those found in ovariectomized control animals. The reduction in serum osteocalcin concentrations in tamoxifen-treated animals, on the other hand, was reduced maximally by about 30% compared to those found in the ovariectomized controls at a dose of 100 micrograms/kg/d. Further reduction in serum osteocalcin beyond this level was not observed with increasing doses of tamoxifen. We conclude that tamoxifen acts as an estrogen agonist with respect to effects on serum osteocalcin levels, but fails to reduce serum levels of osteocalcin to the extent observed with steroidal estrogens.
Bone Biology Research Group, Lilly Research Laboratories, Indianapolis, IN 46285.
D C
DC
Williams
D C
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Paul
L J
LJ
Black
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology*
D013629:Tamoxifen; D015675:Osteocalcin; D004997:Ethinyl Estradiol; D004958:Estradiol