HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT

Abstract

Many members of the androstane series profoundly retarded the growth of a transplanted benign mammary fibroadenoma of the rat; the restraint of tumor growth was in direct proportion to the amount of the administered compound until its maximal effect was achieved. Certain steroids closely related to the androstane inhibitors accelerated the growth of the tumor. These effects of divergent sort depend on the molecular structure of the steroid. The molecular structure of androstane derivatives, which is of high significance in modifying the rate of growth of the benign mammary tumor, consists of multiple components. These include (a) the presence and number of ketone and hydroxyl groups in special orientation at specific sites, (b) the sites of dehydrogenation in the molecule, and (c) the presence, number, and state of hydrogenation of alkyl groups at designated molecular positions. These multiple factors determine whether androstane compounds will inhibit growth of the tumor, enhance it, or fail to influence its growth. The androstane compounds which caused either the restraint or the promotion of tumor growth had the common property of inducing proliferation of the normal mammary epithelium. Two mechanisms are involved in the restraint of growth of mammary fibroadenoma by androstane inhibitors. The primary effect is the abolition of action of phenolic estrogens and progesterone when dihydrotestosterone is administered concurrently, presumably through direct action at the tumor cell level A secondary contributory suppressive effect is the depression of ovarian activity, and consequently of the production of phenolic estrogens and progesterone, by these compounds. Transplanted mammary fibroadenoma in the rat possesses neoplastic traits and also some growth properties of normal mammary epithelium; inhibition of these latter by hormonal methods commonly retarded the growth of the tumor. But in hypophysectomized rats dihydrotestosterone failed to inhibit the growth of a mammary fibroadenoma with unusually low hormonal dependence as determined by functional tests of its growth.