Our long term goals are to understand the interaction between OT and PGs and their importance in the initiation of labor. The principal goal of this proposal is to determine the relationship between the occupancy of OT binding sites in decidua, endometrium and amnion and the production of PGs.
The specific aims are to: 1. Study OT binding sites in decidua, endometrium and amnion with respect to affinity, concentration, ligand specificity, and metal ion requirements. 2. Show the relationship between OT binding and PG release in these tissues, with respect to OT agonists and antagonists. 3. Study the relationship between changes in OT sensitivity of PG release and changes in the concentration of OT receptors. We will study decidua from guinea pigs and rabbits at different stages of pregnancy and guinea pig endometrium during the estrous cycle. 4. Study effects of estrogen and progesterone, administered both in vivo and in vitro, on OT receptor concentrations in guinea pig and rabbit endometrium and cultured human amnion cells. We hope to establish whether steroid-induced changes in receptor concentration are related to changes in the sensitivity of the release of PGs. 5. Establish the validity of using an iodinated OT antagonist, previously shown to bind specifically to OT receptors in. the myometrium, mammary gland and regions of the brain, as a probe for OT receptors in the endometrium, decidua, and amnion. The use of iodinated antagonist would greatly reduce the amount-of tissue needed for subsequent studies. 6. Study physicochemical properties of OT receptors in the endometrium/decidua and possibly amnion. These studies include determination of the functional molecular mass by radiation inactivation studies, the size of the binding unit by photoaffinity cross-linking and solubilization studies, as carried out by us previously with OT receptors in the rat mammary gland. These studies will form the basis for later work elucidating the mechanisms by which OT stimulates PG production.
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