Control of Hormone Receptor Levels and Growth of 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors by Estrogens, Progesterone and Prolactin

Publisher Website
Google Scholar
Abstract
The effect of various hormone treatments was investigated on the growth and hormone receptor levels of hormone-dependent (those which regressed after ovariectomy) dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat. Hormone binding measured in the tumors which remained 5 1/2 wk after ovariectomy was low for estradiol-17.beta. (E2) (0.6 .+-. 0.2 pmol/g tissue), R 5020 [17,21- dimethyl-19-norpregna-4,5-diene-3,20-dione] (0.9 .+-. 0.4 pmol/g tissue) and prolactin (PRL) (0.9 .+-. 0.4% of specific binding). In noncastrated animals, binding values were 2.9 .+-. 0.4 pmol/g tissue, 13.7 .+-. 2.0 pmol/g tissue and 3.2 .+-. 0.3% for E2, R 5020 and PRL, respectively. Administration of progesterone (P) alone (0.5 mg/day) for 3 wk to castrated animals had no effect on tumor size or hormone binding. Treatment with E2 (0.5 .mu.g/day) for the same period of time increased tumor size and hormone binding: E2, 3.0 .+-. 0.7 pmol/g tissue; R 5020, 14.8 .+-. 3.3 pmol/g tissue; PRL, 2.4 .+-. 0.6%. At a daily dose of 2 mg, PRL alone increased tumor size slightly while hormone binding remained low except for that of E2 which was increased to 2.0 .+-. 0.4 pmol/g tissue. Combination of E2 with P or PRL resulted in tumor growth greater than that observed after PRL or E2 alone. The levels of hormone binding present in the tumors at the end of these combined treatments were all increased to levels similar to those obtained with E2 alone. The presence of estrogen receptors in DMBA-induced mammary tumors is a good index of hormone dependency. The levels of this receptor were high under all hormone treatments which led to stimulation of tumor growth. These studies also demonstrate that the concentration of P receptors in DMBA-induced mammary tumors, as well as the response of the tissue to P, depends on E2.