Wade G N, Powers J B
Department of Psychology, University of Massachusetts, Amherst 01003.
Am J Physiol. 1993 Sep;265(3 Pt 2):R559-62. doi: 10.1152/ajpregu.1993.265.3.R559.
Ovariectomized Syrian hamsters were treated with estradiol benzoate (5 micrograms/day for 4 wk), tamoxifen (500 micrograms/day), an antiestrogen that competes with estradiol for central and peripheral estrogen receptors, or both estradiol benzoate and tamoxifen. As expected, estradiol treatment caused significant decreases in body weight and fat content without affecting food intake. Given alone, tamoxifen had no effect on body weight or composition, but when given concurrently, tamoxifen significantly attenuated the effects of estradiol. These results stand in contrast to findings in rats where nonsteroidal antiestrogens, including tamoxifen, mimic the effects of estradiol on body weight and energy metabolism and are completely devoid of any antiestrogenic actions. As in rats, tamoxifen was a potent inhibitor of estrous behavior, whether induced with estradiol alone or with sequential treatment with estradiol and progesterone. Again, as in rats, tamoxifen acted as an antagonist and a weak estrogen agonist on uterine weight. These findings support the notion that the relative agonistic and antagonistic actions of tamoxifen, and other antiestrogens, vary with species and with the estrogen-sensitive endpoint being investigated.
对切除卵巢的叙利亚仓鼠分别给予苯甲酸雌二醇（5微克/天，持续4周）、他莫昔芬（500微克/天）——一种能与雌二醇竞争中枢和外周雌激素受体的抗雌激素药物，或同时给予苯甲酸雌二醇和他莫昔芬。正如预期的那样，雌二醇治疗导致体重和脂肪含量显著下降，但不影响食物摄入量。单独给予他莫昔芬对体重或身体组成没有影响，但同时给予时，他莫昔芬能显著减弱雌二醇的作用。这些结果与在大鼠中的发现形成对比，在大鼠中，包括他莫昔芬在内的非甾体类抗雌激素药物会模拟雌二醇对体重和能量代谢的作用，并且完全没有任何抗雌激素作用。与大鼠一样，无论单独用雌二醇诱导发情行为，还是先后用雌二醇和孕酮诱导发情行为，他莫昔芬都是发情行为的有效抑制剂。同样，与大鼠一样，他莫昔芬对子宫重量起拮抗剂和弱雌激素激动剂的作用。这些发现支持这样一种观点，即他莫昔芬和其他抗雌激素药物的相对激动和拮抗作用因物种以及所研究的雌激素敏感终点而异。
