Though classically considered a WNT signaling intermediary, @entity12401 (b-catenin) can also mediate @entity1176 induction of gonadotropin b subunit ( @entity12101 and @entity12102 ) transcription in the @entity19 gonadotrope-like cell line LbT2. Here, we assessed @entity12401 's role in gonadotropin synthesis in vivo. We used a Cre/lox approach to introduce both gain- and loss-of-function mutations in the @entity19 @entity12401 gene in gonadotrope cells. Gonadotropin production and fertility were normal in @entity12401 knockout @entity19 . Similarly, females harboring a deletion of exon 3 of @entity12401 , which stabilizes the resulting @entity12401 protein, showed normal fertility and gonadotropin synthesis. Interestingly, males with the activating @entity12401 -/\exon 3 mutation exhibited 50% reductions in FSH synthesis and secretion, without a corresponding change in LH. This selective regulation of FSH suggested an alteration in the activin/inhibin/follistatin system. Indeed, @entity12401 -/\exon 3 males showed a 60% increase in serum inhibin B levels and, in culture, their pituitaries exhibited a greater sensitivity to exogenous inhibin than controls. At the same time, pituitary, but not testicular, follistatin (Fst) expression was increased significantly in these @entity19 . Castration normalized FSH levels in @entity12401 -/\exon 3 males to those seen in castrated controls. Paradoxically, pituitaries from @entity12401 -/\exon 3 males exhibited greater basal and activin-stimulated FSH synthesis in vitro. Similarly, @entity12401 -/\exon 3 overexpression potentiated activin A-induced @entity19 @entity12101 promoter activity in LbT2 cells. Together, these results indicate that @entity12401 is dispensable for gonadotropin synthesis in vivo. However, sustained @entity12401 signaling potentiates activin-induced @entity12101 expression in gonadotropes, but this effect is overcome in vivo by enhanced inhibin feedback sensitivity and Fst expression.

b-catenin stabilization in gonadotropes impairs follicle-stimulating hormone synthesis in male XXXX in vivo.

@entity12101 :: ('14308(Tax:10090)', 'Gene') :: ['Fshb'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity12401 :: ('12387(Tax:10090)', 'Gene') :: ['Ctnnb1', 'CTNNB1'] @entity12102 :: ('16866(Tax:10090)', 'Gene') :: ['Lhb'] @entity1176 :: ('MESH:D007987', 'Chemical') :: ['GnRH']
@entity19 :: (10090,Species) :: ['mice']
