9514038 Ing Estrogen is the most powerful hormone within animals and man which, in low doses that work over long times, regulates reproduction and many other body processes. The goal of the proposed research by Dr. Ing is to learn how estrogen acts at the molecular level. One way estrogen enhances its effects is by increasing the protein it binds ("estrogen receptor") within the tissues. The tissues that respond to estrogen. With it, she has demonstrated that estrogen increases estrogen receptor protein and estrogen receptor messenger RNA (mRNA). Contrary to current beliefs in estrogen action, however, estrogen did not enhance the rate of estrogen receptor mRNA synthesis from the estrogen receptor gene. Since proteins, like the estrogen receptor, are made with information encoded in genes (proteins are made from mRNAs which are made from genes), regulation may be occurring at the level of the mRNA instead of the gene. Therefore, her hypothesis is that estrogen decreases the decay of estrogen receptor mRNA to enhance concentrations of estrogen receptor protein in tissues and estrogen responses of animals. The proposed experiments will prove the hypothesis and then determine how it occurs in molecular terms. First, uterine tissues from estrogen-treated and control animals will be cultured and analyzed to determine if estrogen really does stabilize estrogen receptor mRNA. Next, the specific segment of the estrogen receptor mRNA responsible for estrogen-regulated stability will be identified in mutated mRNAs. Finally, the regulatory proteins that bind and act on the estrogen receptor mRNA to stabilize it in the presence of estrogen will be characterized. This insight into the basic action of this powerful hormone will lead to a better understanding of normal reproductive physiology on a molecular level. ***
