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Development of Primordial Follicles in the Hamster: Role of Estradiol-17ß

Departments of Obstetrics and Gynecology (C.W., S.K.R.) and Cellular and Integrative Physiology (S.K.R.), Durham Research Center, University of Nebraska Medical Center, Omaha, Nebraska 68198

Address all correspondence and requests for reprints to: Shyamal K. Roy, Departments of Obstetrics and Gynecology and Cellular and Integrative Physiology, University of Nebraska Medical Center, 984515 Nebraska Medical Center, Omaha, Nebraska 68198-4515. E-mail: skroy{at}unmc.edu.

The role of E₂ on primordial follicle formation was examined by treating neonatal hamsters with 1 or 2 µg estradiol cypionate (ECP) at age postnatal d 1 (P1) and P4 or by in vitro culture of embryonic d 15 (E15) ovaries with 1, 5, or 10 ng/ml estradiol-17ß (E₂). The specificity of E₂ action was examined by ICI 182,780. One microgram of ECP maintained serum levels of E₂ within the physiological range, significantly reduced apoptosis, and stimulated the formation and development of primordial follicles. In contrast, 2 µg ECP increased serum E₂ levels to 400 pg/ml and had significantly less influence on primordial follicle formation. In vivo, ICI 182,780 significantly increased apoptosis and caused a modest reduction in primordial follicle formation. The formation and development of primordial follicles in vitro increased markedly with 1 ng/ml E₂, and the effect was blocked by ICI 182,780. Higher doses of E₂ had no effect on primordial follicle formation but significantly up-regulated apoptosis, which was blocked by ICI 182,780. CYP19A1 mRNA expression occurred by E13 and increased with the formation of primordial follicles. P4 ovaries synthesized E₂ from testosterone, which increased further by FSH. Both testosterone and FSH maintained ovarian CYP19A1 mRNA, but FSH up-regulated the expression. These results suggest that neonatal hamster ovaries produce E₂ under FSH control and that E₂ action is essential for the survival and differentiation of somatic cells and the oocytes leading to the formation and development of primordial follicles. This supportive action of E₂ is lost when hormone levels increase above a threshold.

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