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BOR - Papers in Press, published online ahead of print October 3, 2007.
Biol Reprod 2007, 10.1095/biolreprod.107.063537
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Submitted June 18, 2007
Returned for revision July 15, 2007
Accepted September 28, 2007

Gamete Biology


Regulation of Pcsk6 Expression During the Preantral to Antral Follicle Transition in Mice: Opposing Roles of FSH and Oocytes

Francisco J. Diaz , Koji Sugiura , and John J. Eppig *

* To whom correspondence should be addressed. E-mail: jje{at}jax.org.

Abstract
Several secreted products of the TGFbeta superfamily have important roles during follicular development and are produced by both oocytes and somatic cells (granulosa and theca) in the follicle. The proprotein convertases are a family of seven known proteins that process TGFbeta ligands and other secreted products to their mature active form. The present study examined the regulation of steady-state levels of Pcsk6 mRNA, which encodes a convertase protein known to process members of the TGFbeta superfamily, during mouse follicular development. Pcsk6 mRNA and protein were expressed in preantral but not cumulus or mural granulosa cells. Pcsk6 mRNA levels in preantral granulosa cells were not regulated by growing oocytes of preantral follicles, but were elevated by FSH. Furthermore, Pcsk6 mRNA in preantral granulosa cells was potently suppressed by factor(s) secreted by fully grown oocytes from antral follicles, in part through SMAD2/3-mediated pathways. Oocytes acquired the ability to suppress the steady-state levels Pcsk6 mRNA in granulosa cells during preantral to antral follicle transition. Suppression of Pcsk6 mRNA by oocytes could reflect a change in the mechanism(s) regulating the activity of members of the TGFbeta superfamily.

Key words: Gamete Biology • Cumulus cells • Follicular development • Granulosa cells • Oocyte development





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