Koot R W, Amelink G J, Blankenstein M A, Bär P R
Department of Neurology, University of Utrecht, The Netherlands.
J Steroid Biochem Mol Biol. 1991;40(4-6):689-95. doi: 10.1016/0960-0760(91)90292-d.
Tamoxifen (TX), an oestrogen antagonist, was used to characterize the protective effect of oestradiol (E2) on exercise-related creatine kinase (CK) release from skeletal muscle of the rat. Subcutaneous administration of TX for 3 weeks in female rats had a profound antioestrogen effect as evidenced by a reduced weight of the uterus. The CK release after electrical stimulation of the isolated soleus muscle, previously shown to be E2-dependent, was markedly reduced (30-50%) after treatment with TX; this observation points to an E2-like protective action of TX instead of E2-antagonism. This effect was dose-dependent (0.25-1.00 mg/kg) and was not seen when TX was given shortly (24 h) before the experiments. In ovariectomized females, that show more CK leakage due to the lack of circulating E2, both E2- and TX-treatment resulted in a 60% reduction of the CK leakage. Muscles from male rats, treated with TX, showed a similar response: after contractions the CK release was significantly lower. We conclude that TX, like E2, reduces contraction-induced muscle damage in the rat and, thus, has E2-agonistic properties on skeletal rat muscle.
他莫昔芬(TX)是一种雌激素拮抗剂,被用于研究雌二醇(E2)对大鼠骨骼肌运动相关肌酸激酶(CK)释放的保护作用。对雌性大鼠皮下注射TX 3周具有显著的抗雌激素作用,子宫重量减轻即为证据。先前已证明,电刺激离体比目鱼肌后CK的释放依赖于E2,而用TX治疗后,CK的释放显著减少(30%-50%);这一观察结果表明TX具有类似E2的保护作用,而非E2拮抗作用。这种作用呈剂量依赖性(0.25-1.00mg/kg),且在实验前短时间(24小时)给予TX时未观察到这种效果。在去卵巢雌性大鼠中,由于缺乏循环E2,CK泄漏更多,E2和TX治疗均使CK泄漏减少了60%。用TX处理的雄性大鼠肌肉也表现出类似反应:收缩后CK释放显著降低。我们得出结论,TX与E2一样,可减少大鼠收缩诱导的肌肉损伤,因此,对大鼠骨骼肌具有E2激动特性。