Effects of bromocriptine and tamoxifen on growth and hormone receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.
The role of prolactin (PRL) and estrogen in the growth of 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumors was investigated. Tumor growth was suppressed by both bromocriptine and tamoxifen. Combined administration of ovine PRL and tamoxifen attenuated the inhibitory action of tamoxifen on tumor growth. Serum PRL levels were decreased by both bromocriptine and tamoxifen administration. Estrogen receptors (ER) in tumor tissues were decreased in number by tamoxifen, but not by bromocriptine. Progesterone receptors (PgR) in DMBA-induced mammary tumors were abolished by tamoxifen and significantly reduced by bromocriptine. Combined administration of ovine PRL with tamoxifen attenuated the inhibition of PgR induced by tamoxifen alone, while ER remained undetectable. Specific PRL binding to the liver was significantly reduced by treatment with bromocriptine, tamoxifen and tamoxifen plus ovine PRL, whereas PRL receptors in mammary tumor were not influenced by these drugs. These results suggest that PRL may stimulate DMBA-induced tumor growth independently of ER and that a part of the inhibiting effect of tamoxifen on tumor growth may be explained by the decreased PRL secretion.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000032:analysis* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D011981:Receptors, Prolactin; D013629:Tamoxifen / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011981:Receptors, Prolactin; D013629:Tamoxifen; D001971:Bromocriptine; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin