The sex steroid hormones (estrogen and progesterone) stimulate growth, maturation and the development of new biochemical capacities in their reproductive target organs. These steroids play a major role in maternal physiology and fetal differentiation and their relationships to reproductive tissue malignancy are well established. Although steroid hormones exert major influences on the synthesis of nucleic acid and protein, the biochemical processes by which sex hormones regulate growth and function in target tissues are not yet defined in precise detail. The general objectives of these studies are to define the mechanism of action of reproductive steroid hormones in regulating morphologic differentiation and biochemical specialization in their target tissues. This will be accomplished by coordinating a network of separate investigations in a single experimental animal model system in which specific biochemical events can be studied easily - the chick oviduct. These studies will involve aspects of cell biology, nucleic acid biochemistry and a rather large effort in protein purification. Our emphasis will be directed toward experimental studies on the regulation of nucleic acid and protein synthesis. Our present efforts involve the isolation and purification of nuclear DNA-binding proteins which impart the capacity for gene expression and transcription to target genes for sex steroid hormones. Prevalent hypotheses for steroid action involve the nuclear interaction of promoter and enhancer regulatory factors. Steroid receptors are a major component in the transcription complex responsible for activation of the oviduct egg-white genes. Ultimately the generation of reliable cell-free transcription systems composed of purified reconstituted factors should allow us to define the manner by which sex steroids regulate gene expression and protein synthesis in eucaryotic target cells. It is expected that the understanding derived from this project will be relevant to the biology of the natural reproductive hormones relative to maternal physiology, fetal development and the design of new contraceptive agents. The following proposed studies should also be pertinent to development of more precise theories for the biochemical mechanism of action of hormones in general, and more specifically, steroid sex hormones.
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