title: FOXL2 is involved in the synergy between activin and progestins on the follicle-stimulating hormone β-subunit promoter.
abstract: Differential regulation of gonadotropin hormone production in the pituitary is critical for fertility. Activin and progesterone signaling in gonadotrope cells is important for Fshb gene expression. Previously, we reported that synergy between activin and progestins required the binding of SMAD proteins and the progesterone receptor (PR) to the murine Fshb promoter. In this study, we demonstrate that the FOXL2 transcription factor is also necessary for the full synergistic response between activin and progestins. We show that this synergy occurs in a species-specific manner and that multiple elements in the Fshb promoter that bind forkhead box L2 (FOXL2), SMA/mothers against decapentaplegic homologs (SMAD), and PR are required. Furthermore, we demonstrate that FOXL2 can physically interact with PR and SMAD3. Thus, it is likely that protein-protein interactions among FOXL2, SMAD, and PR recruited to the Fshb promoter play a key role in facilitating Fshb transcription before the secondary FSH surge in rodents.
authors.affiliation: Department of Reproductive Medicine and the Center for Reproductive Science and Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Ghochani
authors.forename: Jasjit K
authors.initials: JK
authors.lastname: Saini
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Mellon
authors.forename: Varykina G
authors.initials: VG
authors.lastname: Thackray
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism*; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D052681:Gonadotrophs / Q000166:cytology / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D051379:Mice; D011372:Progestins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D011980:Receptors, Progesterone / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000378:metabolism; D013045:Species Specificity
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D011372:Progestins; D011980:Receptors, Progesterone; D051900:Smad3 Protein; D028341:Activins; D007987:Gonadotropin-Releasing Hormone