1. FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice.
- Author
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Devillers MM, Petit F, Cluzet V, François CM, Giton F, Garrel G, Cohen-Tannoudji J, and Guigon CJ
- Subjects
- Animals, Anti-Mullerian Hormone blood, Anti-Mullerian Hormone genetics, Aromatase genetics, Aromatase metabolism, Cell Proliferation drug effects, Estradiol biosynthesis, Estradiol pharmacology, Female, Follicle Stimulating Hormone pharmacology, Gene Expression Regulation, Developmental drug effects, Gonadotropins metabolism, Granulosa Cells cytology, Granulosa Cells metabolism, Luteinizing Hormone metabolism, Mice, Inbred C57BL, Ovarian Follicle drug effects, Ovarian Follicle growth & development, Ovarian Follicle metabolism, Ovary drug effects, Receptors, FSH genetics, Receptors, FSH metabolism, Anti-Mullerian Hormone metabolism, Estradiol metabolism, Follicle Stimulating Hormone metabolism, Ovary metabolism
- Abstract
Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature follicle-stimulating hormone (FSH)-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by elevated levels of both gonadotropins and E2. We previously demonstrated in mice that elevated FSH concentrations are necessary to induce E2 production by preantral/early antral follicles through the stimulation of aromatase expression without supporting their growth. However, whether this action of FSH could involve AMH is unknown. Here, we show that Amh mRNA and protein abundance and serum AMH levels are elevated in infantile mouse females, compared with those in adults. By experimentally manipulating FSH and E2 levels in infantile mice, we demonstrate that high FSH concentrations lower Amh expression specifically in preantral/early antral follicles, whereas E2 has no effect. Importantly, treatment of infantile ovaries in organotypic cultures with AMH decreases FSH-mediated expression of Cyp19a1 aromatase, but it does not alter the expression of cyclin D2-mediating granulosa cell proliferation. Overall, our data indicate that the infantile elevation in FSH levels suppresses Amh expression in preantral/early antral follicles, thereby favoring Cyp19a1 aromatase expression and E2 production. Together with recent discoveries that AMH can act on both the hypothalamus and the pituitary to increase gonadotropin levels, this work suggests that AMH is a critical regulator of the gonadotrope axis during the infantile period, thereby contributing to adult reproductive function programming.
- Published
- 2019
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