Elsevier

Steroids

Volume 74, Issue 7, July 2009, Pages 595-601
Steroids

Nongenomic steroid-triggered oocyte maturation: Of mice and frogs

https://doi.org/10.1016/j.steroids.2008.11.010Get rights and content

Abstract

Luteinizing hormone (LH) mediates many important processes in ovarian follicles, including cumulus cell expansion, changes in gap junction expression and activity, sterol and steroid production, and the release of paracrine signaling molecules. All of these functions work together to trigger oocyte maturation (meiotic progression) and subsequent ovulation. Many laboratories are interested in better understanding both the extra-oocyte follicular processes that trigger oocyte maturation, as well as the intra-oocyte molecules and signals that regulate meiosis. Multiple model systems have been used to study LH-effects in the ovary, including fish, frogs, mice, rats, pigs, and primates. Here we provide a brief summary of oocyte maturation, focusing primarily on steroid-triggered meiotic progression in frogs and mice. Furthermore, we present new studies that implicate classical steroid receptors rather than alternative non-classical membrane steroid receptors as the primary regulators of steroid-mediated oocyte maturation in both of these model systems.

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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