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Submitted on May 7, 2004
Accepted on September 9, 2004
Department of Physiology, Medical College of Georgia, 1120 15St., Augusta, GA 30912
* To whom correspondence should be addressed. E-mail: cchaffin{at}mail.mcg.edu.
Granulosa cell proliferation during luteinization and terminal differentiation has historically been assumed to decline rapidly following an ovulatory stimulus. In contrast, terminal differentiation in other cell types has recently been associated with a transient increase in proliferation, suggesting that this may occur in the ovarian follicle. The goal of the current study was to test the hypothesis that an ovulatory stimulus to rats results in additional granulosa cell proliferation before cell cycle arrest. Immature rats were given a single injection of PMSG followed by hCG to initiate periovulatory events. The proportion of granulosa cells in S phase did not change until 12 h after hCG, although the majority of the post-hCG proliferation was localized to cumulus granulosa cells for up to 10 h post-hCG. The expression of cyclin D2 mRNA did not decline until 12 h post-hCG, while both cdk 4 and cdk 6 mRNA increased at 6 h. Protein levels of cyclin D2 and cdk 4 did not change as a result of hCG, while cyclin E increased 6 h after hCG. Kinase activity of cdk 2 dropped markedly by 4 h post-hCG, but a slight increase in activity was evident 6-8 h after hCG. These data suggest that cumulus granulosa cells continue to proliferate for up to 10 h after an ovulatory stimulus, possibly via cyclin E / cdk 2. It is concluded that proliferation is maintained in granulosa cells in the proximity of the oocyte during luteinization of the rat follicle.
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