An important function of estradiol (E2) is to stimulate cell proliferation and to induce synthesis of specific proteins in target cells. Both of these effects are believed to involve changes in the RNA transcriptional program of target cells. Experiments are designed to detect transcriptional changes in cultured human endometrial cells (Ishikawa cell line) in response to physiological concentrations of E2. There are a number of human endometrial cell lines around but few of them actually retain E2 responsiveness. The Ishikawa cell line has been shown to retain its ability to respond: proliferation can be stimulated and specific proteins can be induced. Changes in specific mRNA are essential to these effects. These changes will be studied in a systematic way during the first 24 hours following the addition of E2. If E2 effects on these cells are comparable to those occurring in vivo it might be expected that some genes will be induced soon after exposure, as a direct result of E2 receptor interaction with DNA (primary response). Other gene inductions may not be detected until many hours after E2, their induction requiring a protein induced as part of the primary response. Such responses are sometimes characterized as secondary responses. Experiments are suggested that may lead to detecting whether both kinds of mRNA's are increased in response to E2 in human endometrial cells and begin to study and compare the characteristics of these responses.
