The long term objective of this research is to understand the role of estrogen receptors in the regulation of uterine growth and function by elucidating the important receptors mediated events which are required for estrogen regulation of gene function in target cells. This is to be accomplished by the study of the steroid hormone regulated expression of the marker protein, peroxidase, correlated with estrogen-dependent receptor modulation and chromatin binding and by this means to discover the biologically important details of estrogen action at the molecular level. The plan of attack is to use several experimental systems in the rat, mouse, and hamster and various biologically meaningful hormone treatment protocols to discover the nature of hormonal controls of peroxidase expression, and to relate these changes in marker with the estrogen receptor interaction and its activation, nuclear binding, and chromatin localization, and eventually gene regulation. With antibody to rat uterine peroxidase we will embark on studies to quantitate the hormonal regulation of peroxidase mRNA, immunochemically detectable peroxidase polypeptide and enzyme in order to clarify the nature of the transcriptional, processing, translational and post-translational controls effected by hormones in the uterus. With the newly developed reagents in our laboratory, specifically antibody to the marker peroxidase and antibodies to the estrogen receptor, we have the unique reagents and capability to carry out studies which can clarify the intimate details of the estrogen receptor-mediated regulation of gene expression in the mammalian reproductive tract. These studies can be expected to improve our understanding of the endocrinology of the uterus at the biochemical level.
