Ovulation constitutes one of the single most important events in the perpetuation of a species. Yet, much remains to be learned concerning the complex follicular mechanisms that underlie this phenomenon. Such knowledge would undoubtedly be useful in the development of new approaches to the regulation of fertility and infertility. In response to the pituitary surge in secretion of luteinizing hormone, preovulatory ovine follicles synthesize large quantities of progesterone. The increase in progesterone is associated with decreased follicular production of prostaglandin (PG) E2 and increased production of PGF2Alpha. Of the metabolites of arachidonic acid synthesized by the preovulatory follicle, PGF2Alpha appears to be the leading candidate for the primary role in the process of ovulation. Prostaglandin E2 antagonizes the action of PGF2Alpha in most physiological systems. It is hypothesized that progesterone causes a decrease in the follicular PGE2 to PGF2Alpha ratio by enhancing the activity of PGE2-9-keto-reductase, the enzyme that converts PGE2 to PGF2Alpha. Thus, control of this enzyme could be a very important determinant of ovulation, and may be a link in the ovulatory process that can be effectively manipulated. The objectives of the proposed studies are to determine how progesterone and prostaglandins might interact in the mechanism of ovulation. The ewe will be the experimental model. Specific aims are 1) to examine the effect of inhibition of preovulatory follicular synthesis of progesterone on follicular synthesis of PGE2 and PGF2Alpha; and 2) to determine if progesterone influences the activity of PGE2-9-keto-reductase. Synthesis of progesterone by preovulatory follicles will be suppressed by intrafollicular injection of isoxazol (a specific inhibitor of 3Beta-hydroxysteroid-dehydrogenase, the enzyme that converts pregnenolone to progesterone). Progesterone, PGE2 and PGF2Alpha will be analyzed in follicles by radioimmunoassay. The ability of the preovulatory follicle to convert radioactive PGE2 to PGF2Alpha will be used as an assay of enzymatic activity.