The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism

Abstract

Xenopus laevis oocytes are physiologically arrested at G2 of meiosis I. Resumption of meiosis, or oocyte maturation, is triggered by progesterone. Progesterone-induced Xenopus oocyte maturation is mediated via an extranuclear receptor and is independent of gene transcription. The identity of this extranuclear oocyte progesterone receptor (PR), however, has remained a longstanding problem. We have isolated the amphibian homologue of human PR from a Xenopus oocyte cDNA library. The cloned Xenopus progesterone receptor (xPR) functioned in heterologous cells as a progesterone-regulated transcription activator. However, endogenous xPR was excluded from the oocyte nucleus and instead appeared to be a cytosolic protein not associated with any membrane structures. Injection of xPR mRNA into Xenopus oocytes accelerated the progesterone-induced oocyte maturation and reduced the required concentrations of progesterone. In enucleated oocytes, xPR accelerated the progesterone-induced mitogenactivated protein kinase activation. These data suggest that xPR is the long sought after Xenopus oocyte receptor responsible for progesterone-induced oocyte maturation.

Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation

“…Similarly, we could not enhance progesterone-induced maturation by over-expression of one of the Xenopus PRs, nor could we convincingly attenuate steroidinduced maturation by injection of anti-sense oligonucleotides to mRNAs encoding AR or one of the two PRs (data not shown). Although these results conflict with published reports (4,5), the potential for nonspecific effects in anti-sense experiments likely accounts for this variation.…”

“…T he phenomenon of progesterone-induced maturation of Xenopus oocytes has served as an in vitro experimental model for studying meiosis and cell cycle regulation for over 30 years (1)(2)(3), with recent work implicating the classical nuclear͞cytoplasmic progesterone receptor (PR) as the mediator of these processes (4,5). Although progesterone is a potent promoter of Xenopus oocyte maturation in vitro, little is known about its role in mediating maturation in vivo.…”

“…In mice, ovaries from females lacking the PR gene still contain well-developed follicles with mature oocytes (7), suggesting that progesterone and its receptor are not necessary for oocyte maturation and that other factors are therefore important. Finally, mifepristone (RU486), a potent inhibitor of both mammalian and Xenopus PR-mediated transcription, does not block progesterone-mediated maturation (5), implying that, even in vitro, signaling via the PR may not be the only mechanism behind progesterone-induced maturation.…”

Metazoan oocyte and early embryo development program: a progression through translation regulatory cascades

“…The resumption of meiosis marks the onset of oocyte maturation and is stimulated by progesterone in Xenopus (Bayaa et al 2000;Tian et al 2000) and by gonadotropins in mouse and human (Faiman and Ryan 1967;Rao et al 1974). In almost all vertebrates, nuclear and cytoplasmic changes associated with oocyte maturation are completed by the metaphase of the second meiotic division, when oocytes become arrested for a second time and await fertilization (Sagata 1996).…”

G 2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A

“…[1][2][3]. Progesterone activates the oocyte through a nontranscriptional cytoplasmic signaling pathway that requires one and possibly two types of receptors: XPR1, a conventional transcriptional progesterone receptor that can also initiate cytoplasmic signaling (4,5), and an unidentified G protein-coupled receptor (6)(7)(8). Despite uncertainties about the earliest steps in receptor action, it is well established that progesterone induces two parallel pathways that converge on the activation of cyclin B-cdc2 (Fig.…”