FGF21 contributes to neuroendocrine control of female reproduction.
Preventing reproduction during nutritional deprivation is an adaptive process that is conserved and essential for the survival of species. In mammals, the mechanisms that inhibit fertility during starvation are complex and incompletely understood. Here we show that exposure of female mice to fibroblast growth factor 21 (FGF21), a fasting-induced hepatokine, mimics infertility secondary to starvation. Mechanistically, FGF21 acts on the suprachiasmatic nucleus (SCN) in the hypothalamus to suppress the vasopressin-kisspeptin signaling cascade, thereby inhibiting the proestrus surge in luteinizing hormone. Mice lacking the FGF21 co-receptor, β-Klotho, in the SCN are refractory to the inhibitory effect of FGF21 on female fertility. Thus, FGF21 defines an important liver-neuroendocrine axis that modulates female reproduction in response to nutritional challenge.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Bryn M
BM
Owen
Angie L
AL
Bookout
Xunshan
X
Ding
Vicky Y
VY
Lin
Stan D
SD
Atkin
Laurent
L
Gautron
Steven A
SA
Kliewer
David J
DJ
Mangelsdorf
D000818:Animals; D004734:Energy Metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D007031:Hypothalamus; D007247:Infertility, Female / Q000378:metabolism*; D059648:Kisspeptins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000090265:Klotho Proteins; D007986:Luteinizing Hormone / Q000096:biosynthesis / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011359:Proestrus / Q000502:physiology; D012098:Reproduction; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000378:metabolism
D059648:Kisspeptins; C418622:Klb protein, mouse; D008565:Membrane Proteins; C414620:fibroblast growth factor 21; D014667:Vasopressins; D005346:Fibroblast Growth Factors; D007986:Luteinizing Hormone; D000090265:Klotho Proteins