Reproduction is a complex process regulated by many factors including the ovarian steroids. The broad objective of the proposed studies is to clarify how the ovarian steroids interact with their receptor systems, and to determine how that interaction regulates the morphological and biochemical state of the mammalian oviduct and uterus. A major goal will be to study these interactions in pregnant and pseudopregnant animals. Changes in the compartmentalization of the steroid receptor systems will be correlated with changes in the morphology and secretory activity of the implantation and nonimplantation site endometrium. Data from the pseudopregnant and pregnant animals will be compared to determine what role the conceptus may play in maintaining pregnancy. The steroid receptors will be quantitated using dextran coated charcoal and exchange assays. Morphological changes will be assessed by light and electron microscopy. Secretory activity will be monitored by placing minced endometrial tissue in culture media containing labelled amino acids and sugars and incubated for 24 hours. Culture media will be analyzed by SDS-PAGE or 2-D gel electrophoresis followed by fluorography to identify newly synthesized proteins. An additional aim will be to initiate studies to determine the biological function of a previously identified estrogen-dependent glycoprotein and a progesterone-dependent protein. In vitro techniques will be used to determine if the estrogen-dependent glycoprotein binds to sperm or blastocysts or if it plays some role in the fertilization process. Since the progesterone-dependent protein is synthesized around the time of implantation, studies will be initiated to see if it binds to the blastocyst, or if it has an immunosuppressive or transport function. Another aim of this proposal is to attempt to prepare cDNA probes for the estrogen- dependent glycoprotein and the progesterone-dependent protein. Our ultimate goal is to use these probes to understand the molecular events by which estradiol and progesterone control cells. Another aim of this proposal is to identify oviduct-specific hormone-dependent secretory macromolecules. The data from these proposed studies should provide basic information on the physiology of the oviduct and uterus. This data should enhance our understanding of the reproductive process, and aid clinicians as they attempt to deal knowledgeably with the full reproductive spectrum, namely infertility and contraception.
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