title: Impaired FSHbeta expression in the pituitaries of Foxl2 mutant animals.
abstract: Forkhead box L2 (FoxL2) is required for ovarian development and differentiation. FoxL2 is also expressed in the pituitary where it has been implicated in the development and regulation of gonadotropes, which secrete LH and FSH, the endocrine signals that regulate folliculogenesis in the ovary and spermatogenesis in the testis. Here, we show that FoxL2 is not required for the specification of gonadotropes; the pituitaries of Foxl2 mutant mice contain normal numbers of gonadotropes that express glycoprotein α subunit and LHβ. Whereas the specification of gonadotropes and all other hormonal cell types is normal in the pituitaries of Foxl2 mutant animals, FSHβ levels are severely impaired in both male and female animals, suggesting that FoxL2 is required for normal Fshb expression. The size of the pituitary is reduced in proportion to the smaller body size of Foxl2 mutants, with a concomitant increase in the pituitary cellular density. In primary pituitary cultures, activin induces FSH secretion and Fshb mRNA expression in cells from wild-type mice. In cells from Foxl2 mutant mice, however, FSH secretion is not detected, and activin is unable to drive Fshb expression, suggesting that the mechanism of activin-dependent activation of Fshb transcription is impaired. However, a small number of gonadotropes in the ventromedial region of the pituitaries from Foxl2 mutant mice maintain FSHβ expression, suggesting that a FoxL2- and activin-independent mechanism can drive Fshb transcription. These data indicate that, in addition to its role in the ovary, FoxL2 function in the pituitary is required for normal expression of FSH.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Justice
authors.forename: Amy L
authors.initials: AL
authors.lastname: Blount
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pelosi
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Wylie
authors.initials: W
authors.lastname: Vale
authors.forename: Louise M
authors.initials: LM
authors.lastname: Bilezikjian
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D028341:Activins / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D052681:Gonadotrophs / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009929:Organ Size; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D012333:RNA, Messenger; D051785:Smad Proteins; D028341:Activins; D007986:Luteinizing Hormone; D029404:Activin Receptors