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Paradoxical Action of Activin A on Folliculogenesis in Immature and Adult Mice

Department of Obstetrics and Gynecology, Gunma University School of Medicine, Maebashi, Gunma 371, Japan

Address all correspondence and requests for reprints to: Hideki Mizunuma, Department of Obstetrics and Gynecology, Gunma University School of Medicine, 3–39-22, Showa-machi, Maebashi, Gunma 371, Japan. E-mail: mizunuma{at}news.sb.gunma-u.ac.jp

Activin A is a gonadal protein originally isolated from follicular fluid and is recognized as a local regulator of granulosa cell differentiation. Whether activin A promotes folliculogenesis, however, still remains unclarified. The present study was designed to elucidate the effect of activin A on follicular growth in in vitro follicle culture systems. Preantral follicles, 100–120 µm in diameter, were mechanically isolated from BDF1 hybrid immature mice (11 days old) and adult mice (8 weeks old), then cultured for 4 days in a serum-free medium supplemented with activin A (100 ng/ml), FSH (100 mIU/ml), and a combination of both. Follicular diameter was measured daily, and the amount of estradiol and inhibin released at day 4 was determined by RIA. Preantral follicles collected from immature mice showed a significant increase in diameter when cultured with activin A or both activin A and FSH. FSH alone showed no significant effect on the diameter of follicles from immature mice. In contrast, the diameter of preantral follicles from adult mice significantly increased in response to FSH. Activin A did not stimulate growth of follicles from adult mice, and more interestingly, blocked the effect of FSH. The inhibitory action of activin A was in part restored by co-culture with follistatin (100 ng/ml). These results indicate that activin A is folliculogenetic in the prepubertal mouse, but not in adults.

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