title: FOXL2 Is an Essential Activator of SF-1-Induced Transcriptional Regulation of Anti-Müllerian Hormone in Human Granulosa Cells.
abstract: Anti-Müllerian hormone (AMH) is required for proper sexual differentiation by regulating the regression of the Müllerian ducts in males. Recent studies indicate that AMH could be an important factor for maintaining the ovarian reserve. However, the mechanisms of AMH regulation in the ovary are largely unknown. Here, we provide evidence that AMH is an ovarian target gene of steroidogenic factor-1 (SF-1), an orphan nuclear receptor required for proper follicle development. FOXL2 is an evolutionally conserved transcription factor, and its mutations cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), wherein affected females display eyelid defects and premature ovarian failure (POF). Notably, we found that functional FOXL2 is essential for SF-1-induced AMH regulation, via protein-protein interactions between FOXL2 and SF-1. A BPES-inducing mutant of FOXL2 (290-291delCA) was unable to interact with SF-1 and failed to mediate the association between SF-1 and the AMH promoter. Therefore, this study identified a novel regulatory circuit for ovarian AMH production; specifically, through the coordinated interplay between FOXL2 and SF-1 that could control ovarian follicle development.
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pharmacy, CHA University, Seongnam, Korea.
authors.forename: Miae
authors.initials: M
authors.lastname: Won
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Si Eun
authors.initials: SE
authors.lastname: Park
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, Korea.
authors.forename: Seunghwa
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Park
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
mesh_terms: D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D054339:Steroidogenic Factor 1; D054304:Anti-Mullerian Hormone