Prolactin reverses the inhibitory effects of phammacologi cal doses of androgen on 7,12-dimethylbenz(a)anthracene induced mammary tumor growth

Prolactin reverses the inhibitory effects of phammacologi cal doses of androgen on 7,12-dimethylbenz(a)anthracene induced mammary tumor growth (Quadri, S. K. , Kledzik, G. S., and Meites, J. J. NatI. Cancer Inst., 52: 875-878, 1974). To determine whether this effect is due to an alteration in the ability of the tumor cell to bind prolactin, we have quantitated prolactin receptors in androgen-mesponsive and nonresponsive tumors. Prolactinreceptorswere measured with †̃251-Iabeled ovine prolactin in a subcellulan fraction which reproducibly contained 60 to 80% of the total mecep tompresent in tumor homogenates. Prolactin binding was reversible, reached a steady state in 9 hm,and was com pleted by excess unlabeled prolactin. Prolactin bound to its receptor with a K,, of —1x 10'° M. Growing tumors were biopsied, and matsbearing regmown tumors @eme given in jections of 4 mg testosterone propionate twice a week. Prolactin receptors were reduced in most of the tumors, which regressed after testosterone treatment by an average of 63% compared to the pretreatment biopsy specimens. Nonresponsive tumors and vehicle-injected controls showed no significant alterations in receptor content. This reduction of prolactin receptors is probably insufficient to account for androgen-induced mammary tumor regression.