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The intracellular progesterone receptor (PR) in the mammalian ovary is a part of the physiological pathway that facilitates ovulation. Two PR isoforms (A and B) exist, with different molecular and biological functions. Previous studies have revealed that the cellular ratio of the PR isoforms is important for progesterone-responsive tissues and is under developmental control in different species. However, the relative expression of PR isoforms in the ovary is unknown. In this study, we have demonstrated that: 1) The expression of both PR isoforms in mouse granulosa cells was rapidly up-regulated by hCG treatment and dramatically down-regulated when the granulosa cells were undergoing luteinization. The relative level of protein expression of the A and B form was 2:1 and the highest total PR protein expression was found after hCG stimulation. 2) The expression of PR protein was specific to granulosa cells of periovulatory follicles and was absent in undifferentiated granulosa cells of growing follicles. It was not detected in other cell types, i.e., corpora lutea or any stage of follicles with features of apoptosis. 3) Treatment with the PR antagonist RU 486 in vivo resulted in down-regulation of both isoforms in parallel with increased activation of caspase-3, a decreased level of proliferating cell nuclear antigen (PCNA) and a reduced rate of ovulation. 4) In vitro, the PR antagonists RU 486 and Org 31710 increased internucleosomal DNA fragmentation parallel with a decrease of DNA synthesis in granulosa cells which expressed PR. These results indicate that PR and its isoforms participate in regulation of ovulation, along with suppression of granulosa cell apoptosis and promotion of cell survival in the mouse ovary.
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