MAMMARY STROMA MODULATES HORMONAL RESPONSIVENESS OF MAMMARY EPITHELIUM INVIVO IN THE MOUSE

Several lines of evidence indicate that there may be important stromal influences on epithelial behavior in a number of adult organs. The present studies were undertaken to examine the contribution of mammary gland stroma to mammary epithelial cell hormonal responsiveness in vivo. To accomplish this, mouse mammary epithelium from a developmental state that is not responsive to estrogen (E)-regulation of progesterone receptors (3-week-old) was surgically recombined with mammary stroma from a developmental state that is E-responsive (10-week-old) and vice versa. The recombinants were then tested in vivo for the ability of E to regulate epithelial progesterone receptors. The results demonstrate that when immature nonresponsive epithelium is transplanted to mature stroma of E-responsive mice, the epithelium prematurely acquires E responsiveness. When the converse experiment was carried out, mature E-responsive epithelium retained its responsiveness when transplanted to stroma of immature nonresponsive mice. The contribution of the host systemic milieu to changes observed upon transplantation was also assessed. To do this, mature stroma was transplanted to nonresponsive mice before transplantation with nonresponsive epithelium. Under these conditions, the mature stroma was still able to promote responsiveness. Analysis of mammary gland morphology of the surgical recombinants revealed no significant differences in epithelial structures or organization that could account for the observed differences in hormone responsiveness. From these results we conclude that the local environment of mammary stroma has the capacity to influence mammary epithelial cell behavior and can modulate epithelial hormonal responsiveness in vivo. The mechanisms underlying stromal influences on epithelial behavior remain to be elucidated.