Résumé

PL-01

FGF21: un lien entre reproduction et métabolisme

Pr N. PITTELOUD^a

^a Université de Lausanne, Centre Hospitalier Universitaire Vaudois, Lausanne

Loss-of-function mutations in FGFR1 are a frequent cause of congenital hypogonadotropic hypogonadism (CHH), a severe form of gonadotropin-releasing hormone (GnRH) deficiency, in males and females characterized by absent puberty and infertility. FGFR1 mutations also predispose females to hypothalamic amenorrhea (HA), a milder and reversible form of GnRH deficiency associated with stress and/or energy deficits. FGF21 is an important metabolic regulator, which signals through a complex of FGFR1c with its co-receptor ß-Klotho. Interestingly, female Fgf21 transgenic (Tg) mice are resistant to high-fat diet and exhibit GnRH deficiency and infertility. We further demonstrated that loss-of-function KLB mutations underlie congenital GnRH deficiency while Klb-/- mice exhibit delayed puberty supporting a role for KLB in reproduction. These findings highlight FGF21 as an important link between metabolism and reproduction.

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