The ovarian steroid hormone, estradiol, regulates physiology and behavior by actions in the brain. Estradiol binds to intracellular protein receptors found in target neurons within the specific neural brain regions. These steroid-receptor complexes then bind to acceptor sites in the nucleus to alter gene expression (i.e. induction of RNA and protein synthesis). It is the believed that the increase and decrease of proteins resulting from this steroid-receptor interaction is the primary mechanism of action of the hormone. While many of the physiological, morphological and behavioral effects induced by estradiol can be accounted for by this mechanism, recent immunocytochemical studies have identified steroid hormone receptors in the extranuclear regions of the target neurons. This strongly suggests that the hormone also acts through a nongenomic process. Dr. Blaustein will identify other possible sites within neurons at which estradiol acts. Since at the light microscopic level distinct cellular localization can not be readily identified, he will develop an electron microscopic, ultrastructural immunocytochemical technique. Using this technique, Dr. Blaustein will determine the extranuclear organelles with which the steroid receptors are associated. These anatomical studies will significantly enhance our understanding of the cellular mechanisms of action of this hormone. A number of studies have linked estradiol with the occurrence of various types of cancers. A better understanding of the mechanisms of action could eventually lead to improved treatments and possible cures for these life threatening estrogen-related diseases.
