title: FSH and its second messenger cAMP stimulate the transcription of human anti-Müllerian hormone in cultured granulosa cells.
abstract: Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance, a member of the TGF-ß family, is responsible for the regression of Müllerian ducts in the male fetus. In females, AMH is synthesized by granulosa cells of preantral and small antral follicles, and production wanes at later stages of follicle maturation. Using RT-PCR in luteal granulosa cells in primary culture and reporter gene techniques in the KK1 granulosa cell line, we show that FSH and cAMP enhance AMH transcription, and LH has an additive effect. Gonadotropins and cAMP act through protein kinase A and p38 MAPK signaling pathways and involve the GATA binding factor-4 and steroidogenic factor-1 transcription factors, among others. The expression profile of AMH and the dynamics of serum AMH after gonadotropin stimulation have been interpreted as a down-regulating effect of FSH upon AMH production by granulosa cells. The specific effect of gonadotropins upon granulosa cells may be obscured in vivo by the effect of FSH upon follicular maturation and by the presence of other hormones and growth factors, acting individually or in concert.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 782, 32 rue des Carnets, 92120 Clamart, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Taieb
authors.forename: Michaël
authors.initials: M
authors.lastname: Grynberg
authors.forename: Alice
authors.initials: A
authors.lastname: Pierre
authors.forename: Nassim
authors.initials: N
authors.lastname: Arouche
authors.forename: Perrine
authors.initials: P
authors.lastname: Massart
authors.forename: Corinne
authors.initials: C
authors.lastname: Belville
authors.forename: Laetitia
authors.initials: L
authors.lastname: Hesters
authors.forename: René
authors.initials: R
authors.lastname: Frydman
authors.forename: Sophie
authors.initials: S
authors.lastname: Catteau-Jonard
authors.forename: Renato
authors.initials: R
authors.lastname: Fanchin
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Josso
authors.forename: Rodolfo A
authors.initials: RA
authors.lastname: Rey
authors.forename: Nathalie
authors.initials: N
authors.lastname: di Clemente
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D017930:Genes, Reporter; D006062:Gonadotropins / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D006080:Ovarian Follicle / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D006062:Gonadotropins; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases