Nongenomic steroid-triggered oocyte maturation: Of mice and frogs
Introduction
In nearly all vertebrates, oocytes are arrested in prophase I of meiosis until just prior to ovulation, when the gonadotropin luteinizing hormone (LH) binds to G protein-coupled receptors in ovarian follicles to unleash a myriad of signals that ultimately trigger oocytes to re-enter the cell cycle in a process called maturation. Oocytes progress through meiosis to metaphase II, at which point they again arrest until after fertilization, when meiosis is completed [1]. A long-standing model system to study oocyte maturation has been Xenopus laevis [2], [3], [4]. Xenopus oocytes remain in meiotic arrest after removal from the ovary, but can be induced to re-enter the cell cycle in response to multiple steroids. Steroid-triggered maturation of X. laevis oocytes occurs completely independent of transcription, because: (1) very little transcription occurs during the maturation process; (2) addition of transcriptional inhibitors has no effect on steroid-mediated maturation in vitro; and (3) removal of nuclei from oocytes has no effect on steroid-triggered cytoplasmic signals associated with maturation. Since transcription plays no role in the meiotic process, steroid-triggered Xenopus oocyte maturation serves as an ideal physiologic model for studying transcription-independent, or nongenomic, steroid signaling.
Importantly, while significant progress has been made in identifying the steroids, steroid receptors, and intracellular signaling pathways that regulate oocyte maturation in X. laevis, the relevance of steroids in regulating mammalian oocyte maturation has remained controversial. Here we provide a brief overview of meiotic progression in both frogs and mouse oocytes, and present novel data implicating classical steroid receptors as important regulators of steroid-triggered maturation in both systems.
Section snippets
Androgens are the physiologic mediators of Xenopus oocyte maturation
As mentioned in the introduction, X. laevis has served as an excellent experimental model for studying maturation and cell cycle regulation. The advantage of the Xenopus model is the ease of isolating large numbers of oocytes for over-expression and knockdown studies, as well as for assaying signals associated with meiosis (e.g., changes in cAMP, activation of MAPK and CDK cascades) [2], [3], [4], [5]. In addition, isolated Xenopus oocytes remain in meiotic arrest until stimulated by steroid [4]
Steroid-triggered mammalian oocyte maturation
While similar intracellular signaling pathways regulate meiotic arrest in frogs and mammals (e.g., GPR3, cAMP, and Gαs) the role of steroids in triggering mammalian oocyte maturation has remained controversial. Some early studies suggested that steroids were not necessary for rodent oocyte maturation, as inhibitors of steroidogenesis appeared to have minimal effect on gonadotropin-mediated maturation [44], [45], [46]. In contrast, other studies found that inhibitors of steroidogenesis did
Conclusions
In summary, G protein signaling plays a critical role in maintaining meiotic arrest in vertebrate oocytes, mainly by stimulating adenylyl cyclase and increasing intracellular cAMP. However, the nature of this signaling can vary between animals, depending upon the expression of G protein-coupled receptors, G proteins, and adenylyl cyclases within the oocytes. Androgens appear to be the primary physiologic mediators of oocyte maturation in X. laevis, signaling through classical receptors in a
Acknowledgements
This work was supported by the NIH (DK59913) and the March of Dimes Foundation (FY05-78).
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