Steroid-induced maturation of Xenopus oocytes has long served as a model for studying meiosis. Progesterone has been considered the relevant steroid controlling maturation, perhaps through interactions with classical progesterone receptors. In this study, we provide evidence that androgens, rather than progesterone, are the physiologic mediators of Xenopus oocyte maturation. Androgens were equal or more potent activators of maturation in vitro relative to progesterone and were significantly more abundant in the serum and ovaries of -human chorionic growth hormone-stimulated frogs. Androgen action appeared to be mediated by classical androgen receptors (ARs) expressed in oocytes, as androgen-induced maturation and signaling was specifically attenuated by AR antagonists. Interestingly, we found that progesterone was rapidly converted to the androgen androstenedione in isolated oocytes by the enzyme CYP17, suggesting that androgens may be promoting maturation even under conditions typical for ''progesterone-mediated'' maturation assays. Androgens are thought to play an important role in ovarian development as well as pathology, and signaling through the AR may prove to be a major regulatory mechanism mediating these processes.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 (1-3), 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 other animals, progesterone does not appear to be the primary physiologic mediator of oocyte maturation. For example, oocyte maturation in fish is mediated by the progesterone metabolite 17␣, 20-dihydroxyprogesterone (6). 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.In an effort to clarify the physiologic importance of progesterone in Xenopus oocyte maturation, we measured the serum and ovarian steroid content of female frogs injected with -human chronic growth hormone (-hCG). We show that progesterone is barely detectable in the serum and ovaries of these animals but that androgen concentrations are Ͼ10 times higher than that of progesterone. Further, we demonstrate that oocytes are equally or more sensitive to signaling by androstenedione (AD) and testosterone than progesterone. We identify classical Xenopus androgen receptors (ARs) in oocytes and show t...