Estrogens and progestins are two key components in mammalian reproduction. hese hormones with their receptors provide an interlocking and coordinated syste that regulates several tissues critical for female reproduction. One essential requirement in this system is for the estrogen/receptor complex to regulate he availability of the progesterone receptor (PR). In a strain of cells devel ed in our laboratory, Rat1+ER cells, the estrogen receptor (ER) complex is nec sary and sufficient to cause the expression of the previously silent PR gene. T s takes place in a cell that normally does not express either the ER or PR ge s. It appears to be dependent on the stable transfection of the cells with the R because transient transfection does not yield the same results. These cell provide a unique system for studying the new expression of an estrogen-regu ted gene. It should also make possible quantitative studies on the time course f the induction of the PR gene as well as the relationship of estrogen occupa y of the ER to the response of the PR gene. Since the response of the PR gene apparently involves some changes in the accessibility of the regulatory regions of the PR gene to the ER, changes i chromatin structure will also be a focus of our studies. Again, the time c rse of change in chromatin structure in relationship to changes in transcriptio rate of the PR gene will be a major area of study. Finally, all the studies noted above have as a key component the interactio of the ER with regulatory sequences of DNA or estrogen response elements (ERE) Studies of the interaction of the ER with EREs have been limited by the availability of physical techniques that are useful using low concentration of receptor and that can give kinetic measurements of the interaction of the receptor with the DNA. Fluorescent anisotropic spectrophotometry appears t be a procedure of promise that we will use to study DNA/receptor interactions.
| Gorski, J; Hansen, J C (1987) The ""one and only"" step model of estrogen action. Steroids 49:461-75 |
