Williams D C, Paul D C, Black L J
Bone Biology Research Group, Lilly Research Laboratories, Indianapolis, IN 46285.
Bone Miner. 1991 Sep;14(3):205-20. doi: 10.1016/0169-6009(91)90023-s.
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.
在接受了35天治疗的去卵巢大鼠中，检测其血清骨钙素水平。这些大鼠分别接受了雌激素（口服乙炔雌二醇或皮下注射17β-雌二醇）或抗雌激素化合物他莫昔芬（口服和皮下注射）治疗。他莫昔芬是一种非甾体化合物，在几种生物学模型中具有混合的激动剂/拮抗剂作用，但通常被称为“抗雌激素”。与雌激素一样，给予他莫昔芬会导致试验期间动物体重增加和股骨长度增加减少，并且与去卵巢对照动物相比，股骨远端干骺端的骨密度更高。与去卵巢对照大鼠血清中的水平相比，雌激素和他莫昔芬均导致血清骨钙素呈剂量依赖性降低；然而，与雌激素相比，他莫昔芬的效力和效果均降低。在整个雌激素剂量范围内，血清骨钙素水平呈线性下降，在测试的最高剂量（400微克/千克/天乙炔雌二醇；100微克/千克/天17β-雌二醇）下，与去卵巢对照动物相比，骨钙素水平降低了45%-50%。另一方面，在剂量为100微克/千克/天时，与去卵巢对照动物相比，他莫昔芬治疗动物的血清骨钙素浓度最大降低约30%。随着他莫昔芬剂量的增加，未观察到血清骨钙素进一步降低。我们得出结论，就对血清骨钙素水平的影响而言，他莫昔芬作为一种雌激素激动剂，但不能将血清骨钙素水平降低到甾体雌激素所观察到的程度。
