Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor.
The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000097:Acetonitriles / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes; D004334:Drug Administration Schedule; D004873:Ergolines / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000502:physiology; D010546:Perphenazine / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology
D000097:Acetonitriles; D001551:Benz(a)Anthracenes; D004873:Ergolines; D004967:Estrogens; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D010546:Perphenazine