Shigaki N, Kimura M, Takano S, Fujino N, Akagi M
Second Department of Surgery, Kumamoto University Medical School, Japan.
Jpn J Surg. 1987 Sep;17(5):395-401. doi: 10.1007/BF02470640.
Daily injections of 100 micrograms 17 beta-estradiol, or 250 micrograms tamoxifen, for 10 days led to a regression of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor. Estrogen receptor (ER), progesterone receptor (PgR), and prolactin receptor (PRL-R) in the regressed tumor were significantly reduced in the estrogen-treated rats. ER and PRL-R were low but PgR increased significantly in the tumor of the tamoxifen-treated rats. A single administration of 100 micrograms estradiol induced a transient decrease of ER and PRL-R, and an increase of PgR, in the DMBA-tumor. Similar decreases in ER and PRL-R and the increase of PgR were observed 8 hours after the 5th injection of 100 micrograms estradiol--a time when the tumor had already regressed. These results suggest that high dose-estrogen has a direct inhibitory effect on the concentration of both ER and PRL-R in the DMBA-tumor, and that this effect might be accumulative with repeated administrations. It is unlikely that the inhibition of the estrogenic effect caused by loss of ER is the sole mechanism of the regression of the DMBA-tumor, since the increased synthesis of PgR as a marker of estrogen action was observed even after the ER-reduction and tumor-regression.
连续10天每天注射100微克17β-雌二醇或250微克他莫昔芬，可使7,12-二甲基苯并(a)蒽（DMBA）诱导的大鼠乳腺肿瘤消退。在雌激素处理的大鼠中，消退肿瘤中的雌激素受体（ER）、孕激素受体（PgR）和催乳素受体（PRL-R）显著减少。在他莫昔芬处理的大鼠肿瘤中，ER和PRL-R较低，但PgR显著增加。单次给予100微克雌二醇可使DMBA肿瘤中的ER和PRL-R短暂降低，PgR增加。在第5次注射100微克雌二醇8小时后观察到ER和PRL-R有类似降低以及PgR增加，此时肿瘤已经消退。这些结果表明，高剂量雌激素对DMBA肿瘤中ER和PRL-R的浓度有直接抑制作用，且这种作用可能随着重复给药而累积。ER缺失导致雌激素作用受抑制不太可能是DMBA肿瘤消退的唯一机制，因为即使在ER减少和肿瘤消退后，作为雌激素作用标志物的PgR合成仍增加。
