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(569) NONGENOMIC EFFECTS OF STEROIDS ON THE MATURATION OF MOUSE OOCYTES. Gill, Arvind1, Jamnongjit, Michelle1, Hammes, Stephen1, 1 University of Texas Southwestern Medical Center, Dallas, Texas ABSTRACT- Female fertility relies upon precise regulation of oocyte meiosis as well as direct communication between oocytes and surrounding follicular cells. Oocytes are arrested in prophase I of meiosis until ovulation, when meiosis, or maturation, is triggered to resume. Little is known about the ovarian signals that inhibit or promote oocyte maturation in mammals. We have recently shown that androgens and estrogens promote maturation of mouse oocytes arrested in meiosis in vitro. This process is nongenomic, and is associated with mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 1(CDK1 or cdc2) activation. Further, steroid-induced oocyte maturation seems to involve signaling at least in part via classical steroid receptors present in the oocytes. Of the steroids examined, testosterone was the most potent promoter of maturation, as compared to estradiol and progesterone. Flutamide and ICI 182,780, classical steroid receptor antagonists, inhibited testosterone- and estradiol- mediated activation of MAPK, respectively, but not spontaneous maturation. Also, R1881, a potent promoter of AR-mediated transcription, did not promote maturation; rather, it inhibited non-genomic testosterone-mediated signaling in oocytes, suggesting that R1881 may serve as a selective androgen receptor modulator (SARM). Finally, ovarian testosterone and estradiol levels markedly increased just prior to ovulation, suggesting sex steroids act as physiological mediators in the maturation of oocytes. We propose a model, whereby steroids may be acting in a release of inhibition fashion. Constitutive inhibitory signals within the ovary hold meiosis in prophase I. Just prior to ovulation, the gonadotropin surge might promote the production of steroids (mainly testosterone and estradiol), which in turn trigger signals that overcome this meiotic inhibition, thereby promoting maturation and subsequent ovulation to occur. Our results suggest that steroids may participate in the follicular cell/ oocyte cross talk that regulates follicular growth. Furthermore, nongenomic androgen signaling in oocytes may be contributing to the polycystic phenotype induced by excess androgens in women, by promoting the growth of multiple follicles while preventing the development of dominant ones. KEY WORDS: oocytes, meiosis, maturation, ovary |
