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Regular Article |
a Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton, Oregon 97006
b Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
ABSTRACT
Progesterone produced in response to the midcycle gonadotropin surge is essential for ovulation and luteinization of the primate follicle. Because cell-cycle arrest is associated with the initiation of luteinization, this study was designed to determine the dynamics and regulation of granulosa cell proliferation by gonadotropin and progesterone during the periovulatory interval in the primate follicle. Granulosa cells or ovaries were obtained from macaques undergoing controlled ovarian stimulation either before (0 h) or as long as 36 h following the administration of an ovulatory hCG bolus with or without a 3ß-hydroxysteroid dehydrogenase inhibitor with or without a nonmetabolizable progestin. The percentage of cells staining positive for Ki-67, a nuclear marker for cell proliferation, decreased (P < 0.05) within 12 h of hCG administration in a steroid-independent manner. Levels of cyclin D2 and E mRNA did not decline during the periovulatory interval; however, cyclin B1 mRNA was reduced significantly by 12 h. Steroid depletion increased (P < 0.05) cyclin B1 mRNA at both 12 and 36 h post-hCG and was reversible by progestin replacement at 36 h. The cyclin-dependent kinase inhibitor p21Cip1 was transiently increased 12 h post-hCG, whereas p27Kip1 mRNA levels increased at 36 h in a steroid-independent fashion. These data suggest that a gonadotropin bolus inhibits mitosis in granulosa cells early (12 h) in the periovulatory interval, whereas progesterone may play a later, antiproliferative role in luteinized cells of primates.
First decision: 25 January 2001.
1 Supported by NIH/NICHD HD20869, U54 HD18185 as part of the Specialized Cooperative Centers Program in Reproductive Research, HD8302, and RR00163.
2 Correspondence: Richard L. Stouffer, Division of Reproductive Sciences, Oregon Regional Primate Research Center, 505 NW 185th St., Beaverton, OR 97006. FAX: 503 690 5563; stouffri{at}ohsu.edu
3 Current address: Department of Physiology, Medical College of Georgia, Augusta, GA 30912.
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