Correlation between in vitro growth and regulation of estrogen and progesterone receptors in rat mammary epithelial cells.

The present studies examine 1) the effect of enzymatic cell dissociation on the level of cytosolic estrogen receptor (ER) and progesterone receptor (PR) for normal rat mammary tissue, 2) the concentrations of ER and PR in rat mammary epithelial (RME) cells cultured within collagen gel, and 3) correlations that may exist between receptor concentration and cultured RME cell proliferation after hormonal stimulation in vitro. After cell dissociation, ER was present in mammary cells at higher concentrations than those found in the whole gland, whereas PR concentrations were similar to those in the whole gland. As characterized by Scatchard analysis, PR and, to a lesser extent, ER can be maintained in cells cultured in serum-free medium within a collagen gel matrix. ER is apparently functional at relatively low levels, since estradiol did induce PR synthesis, and cytosolic ER was reduced by estrogen administration. However, estradiol had no mitogenic effect on RME cells in this system, supporting the hypothesis that there may be a dichotomy between estrogen's effect on growth and progesterone receptor synthesis. PRL plus progesterone act synergistically to induce cell proliferation in our system, and this correlates with increased concentrations of progesterone receptors. Thus, the collagen gel system appears to provide a useful in vitro model for the study of receptor regulation and cell proliferation.