PROLACTIN RECEPTORS AND ANDROGEN-INDUCED REGRESSION OF 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED MAMMARY-CARCINOMA

Abstract

Prolactin reverses the inhibitory effects of pharmacological doses of androgen on 7,12-dimethylbenz(a)anthracene induced [rat] mammary tumor growth. To determine whether this effect is due to an alteration in the ability of the tumor cell to bind prolactin, prolactin receptors were quantitated in androgen-responsive and nonresponsive tumors. Prolactin receptors were measured with 125I-labeled ovine prolactin in a subcellular fraction which reproducibly contained 60-80% of the total receptor present in tumor homogenates. Prolactin binding was reversible, reached a steady state in 9 h and was completed by excess unlabeled prolactin. Prolactin bound to its receptor with a Kd of .apprx. 1 .times. 10-10 M. Growing tumors were biopsied, and rats bearing regrown tumors were given injections 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.