Evidence That Androgens are the Primary Steroids Produced by Xenopus laevis Ovaries and May Signal through the Classical Androgen Receptor to Promote Oocyte Maturation

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-11, Vol.98 (24), p.13728-13733
• Main Authors: Lutz, L. B., Cole, L. M., Gupta, M. K., Kwist, K. W., Auchus, R. J., Hammes, S. R.
• Format: Article
• Language: English
• Subjects: Androgen Receptor Antagonists; Androgen receptors; Androgens; Androgens - biosynthesis; Androgens - metabolism; androstenedione; Androstenedione - metabolism; Animals; Base Sequence; Biological Sciences; Cells, Cultured; Cellular biology; Complementary RNA; COS cells; CYP17 protein; DNA, Complementary; Ethanol; Female; Freshwater; Intracellular Fluid - metabolism; Molecular Sequence Data; Oocytes; Oocytes - cytology; Oocytes - physiology; Ovaries; Ovary - metabolism; Plasmids; Progesterone - metabolism; Receptors, Androgen - metabolism; Reproductive system; Reptiles & amphibians; Signal Transduction; Steroid 17-alpha-Hydroxylase - genetics; Steroid 17-alpha-Hydroxylase - metabolism; Steroids; Steroids - biosynthesis; Steroids - metabolism; Testosterone; Xenopus; Xenopus laevis; Xenopus laevis - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.241471598

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 β-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.