The long term objective of this proposal is to elucidate local paracrine mechanisms which regulate and govern functional responses of the ovary. The past several years of support show that local regulation of the ovary is closely linked to the pro- and antigondotropic actions of adenosine and prostaglandins, respectively. These studies show that adenosine may be the long sought oocyte maturation inhibitor (OMI) in the follicle, that adenosine may play a role in follicular atresia because it augments granulosa cell responses to LH over FSH, and that adenosine may be a luteotropic modulator in the corpus luteum because it amplifies responses to LH and blocks the luteolytic actions of PGF2a.
The aims of this proposal are therefore: 1. To characterize the mechanism of adenosine action on inhibition of oocyte maturation and to substantiate that adenosine is OMI. 2. To elucidate the intracellular site and mechanism of adenosine action in the luteal cell. 3. To elucidate the post-cyclic AMP site of PGF2a-inhibition of progesterone biosynthesis in the luteal cell. 4. To evaluate the physiological basis for a functional role of adenosine in the ovary. 5. To explore if adenosine may modulate endocrine and functional responses in other cells of the reproductive tract. The methodology utilized in these studies will include isolation, enrichment and culture of ovarian cells such as the cumulus-enclosed oocyte, the denuded oocyte, granulosa, luteal and androgen secreting cells. Adenine purines, metabolites of arachidonic acid and ovarian products will be measured by RIA and HPLC. Oocyte maturation will be scored by light microscopy. Pharmacoglogical analysis of purine receptors in the oocyte will be assessed with purine analogs. The intraluteal site of adenosine and prostaglandin mediators will be studied in isolated mitochondria. Research in this novel area will provide a greater understanding of endocrine regulation and control of the ovary and advance understanding of purine and prostaglandin physiology. Moreover, the information derived from this research may result in heretofore unrecognized avenues for the therapeutic control of reproductive processes in health and disease.
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