Branham W S, Leamons M L, Sheehan D M
Department of Health and Human Services, National Center for Toxicological Research, Jefferson, AR 72079.
J Steroid Biochem. 1988 Feb;29(2):153-9. doi: 10.1016/0022-4731(88)90260-9.
The estrogen antagonists tamoxifen and monohydroxytamoxifen are also classified as partial estrogen agonists. In infantile rats, estradiol induced a single peak of uterine ODC activity at 6h following injection regardless of the extent of induction by various estradiol doses. By contrast, the timing of the ODC activity peak induced by tamoxifen and monohydroxytamoxifen was highly dependent upon the dosing conditions and was delayed to 18 h at lower tamoxifen doses. In immature rats, tamoxifen and monohydroxytamoxifen induced two peaks of uterine ODC activity resembling those induced by estradiol. Both ODC activity peaks were delayed by 9 h, without decreases in peak heights, by a 50-fold tamoxifen dose reduction. In all experiments the initial appearance of antiestrogen- and estradiol-induced ODC activity corresponded to initial uterine wet weight gain regardless of dosing condition. Thus, when dose-related temporal shifts are taken into account, tamoxifen and monohydroxytamoxifen are complete agonists with respect to induction of uterine weight gain and ODC activity.
雌激素拮抗剂他莫昔芬和单羟基他莫昔芬也被归类为部分雌激素激动剂。在幼鼠中,无论不同剂量雌二醇的诱导程度如何,雌二醇在注射后6小时诱导子宫鸟氨酸脱羧酶(ODC)活性出现一个峰值。相比之下,他莫昔芬和单羟基他莫昔芬诱导的ODC活性峰值时间高度依赖于给药条件,在较低的他莫昔芬剂量下延迟至18小时。在未成熟大鼠中,他莫昔芬和单羟基他莫昔芬诱导子宫ODC活性出现两个峰值,类似于雌二醇诱导的峰值。通过将他莫昔芬剂量降低50倍,两个ODC活性峰值均延迟9小时,且峰值高度未降低。在所有实验中,无论给药条件如何,抗雌激素和雌二醇诱导的ODC活性的最初出现都与子宫湿重增加的最初情况相对应。因此,当考虑到剂量相关的时间变化时,就子宫重量增加和ODC活性的诱导而言,他莫昔芬和单羟基他莫昔芬是完全激动剂。