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Anti-Müllerian Hormone Attenuates the Effects of FSH on Follicle Development in the Mouse Ovary

Departments of Endocrinology and Reproduction (A.L.L.D., M.J.G.G., P.K., B.K., F.H.J., J.T.J.U., J.A.G., A.P.N.T.) and Internal Medicine (F.H.J.), Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands 3000; Departments of Pathology (T.R.K., M.M.M.,), Molecular and Cell Biology (T.R.K., M.M.M.), and Molecular and Human Genetics (M.M.M.), Baylor College of Medicine, Houston, Texas 77030; and N.V. Organon, Department of Pharmacology (U.M.R.), Oss 5340 BH, The Netherlands

Address all correspondence and requests for reprints to: Axel P. N. Themmen, Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: themmen{at}endov.fgg.eur.nl

Although ovarian follicle growth is under the influence of many growth factors and hormones of which FSH remains one of the most prominent regulators. Therefore, factors affecting the sensitivity of ovarian follicles to FSH are also important for follicle growth. The aim of the present study was to investigate whether anti-Müllerian hormone (AMH) has an inhibitory effect on follicle growth by decreasing the sensitivity of ovarian follicles to FSH. Furthermore, the combined action of AMH and FSH on ovarian follicle development was examined. Three different experiments were performed. Using an in vitro follicle culture system it was shown that FSH-stimulated preantral follicle growth is attenuated in the presence of AMH. This observation was confirmed by an in vivo experiment showing that in immature AMH-deficient females, more follicles start to grow under the influence of exogenous FSH than in their wild-type littermates. In a third experiment, examination of the follicle population of 4-month-old wild-type, FSHß-, AMH-, and AMH-/FSHß-deficient females revealed that loss of FSH expression has no impact on the number of primordial and preantral follicles, but the loss of inhibitory action of AMH on the recruitment of primordial follicles in AMH-deficient mice is increased in the absence of FSH. In conclusion, these studies show that AMH inhibits FSH-stimulated follicle growth in the mouse, suggesting that AMH is one of the factors determining the sensitivity of ovarian follicles for FSH and that AMH is a dominant regulator of early follicle growth.

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