Abstract
Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty. Accordingly, we report higher levels of pituitary AMH receptor transcripts in immature females. We show that AMH is functionally coupled to the Smad pathway in LβT2 gonadotrope cells and dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action. We report that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females. Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins. Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activins / genetics
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Activins / metabolism
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Animals
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Animals, Newborn
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Anti-Mullerian Hormone / genetics*
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Anti-Mullerian Hormone / metabolism
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Bone Morphogenetic Protein 2 / genetics
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Bone Morphogenetic Protein 2 / metabolism
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Cell Line
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Female
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Follicle Stimulating Hormone / genetics*
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Follicle Stimulating Hormone / metabolism
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Gene Expression Regulation, Developmental
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Gonadotrophs / cytology
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Gonadotrophs / metabolism*
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Gonadotropin-Releasing Hormone / genetics
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Gonadotropin-Releasing Hormone / metabolism
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Hypothalamus / metabolism
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Luteinizing Hormone / genetics
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Luteinizing Hormone / metabolism
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Male
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Pituitary Gland, Anterior / cytology
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Pituitary Gland, Anterior / growth & development
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Pituitary Gland, Anterior / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptors, Peptide / genetics*
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Receptors, Peptide / metabolism
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Receptors, Transforming Growth Factor beta / genetics*
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Receptors, Transforming Growth Factor beta / metabolism
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Sex Characteristics*
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Sexual Maturation
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Signal Transduction
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Smad Proteins / genetics
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Smad Proteins / metabolism
Substances
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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RNA, Messenger
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Receptors, Peptide
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Receptors, Transforming Growth Factor beta
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Smad Proteins
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anti-Mullerian hormone receptor
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Activins
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Gonadotropin-Releasing Hormone
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Anti-Mullerian Hormone
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Luteinizing Hormone
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Follicle Stimulating Hormone