Reduction of estrogen and prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor by high doses of estrogen.
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.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000032:analysis* / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000187:drug effects; D011981:Receptors, Prolactin / Q000032:analysis / Q000187:drug effects*; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011981:Receptors, Prolactin; D013629:Tamoxifen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene