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Submitted on August 27, 2003
Accepted on October 15, 2003
1 Department of Internal Medicine, Division of Endocrinology and Metabolism, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390-8857, USA
* To whom correspondence should be addressed. E-mail: stephen.hammes{at}utsouthwestern.edu.
Normal fertility in females depends upon precise regulation of oocyte meiosis. Oocytes are arrested in prophase I of meiosis until just before ovulation, when meiosis, or maturation, is triggered to resume. While sex steroids appear to promote maturation in fish and amphibians, the factors regulating mammalian oocyte maturation have remained obscure. We show here that, similar to lower vertebrates, steroids may play a role in promoting the release of meiotic inhibition in mammals. Specifically, testosterone induced maturation of mouse oocytes arrested in meiosis, as well as activation of mitogen-activated protein kinase and cyclin dependent kinase 1 signaling. These responses appeared to be transcription-independent, and might involve signaling through classical androgen receptors expressed in the oocytes. Our results are the first to show that sex steroids can modulate meiosis in mammalian oocytes, and suggest a model whereby dominant ovarian follicles in mammals may produce sufficient androgen and/or other steroids to overcome constitutive inhibitory signals and allow oocyte maturation and subsequent ovulation to occur.
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