FGF21 contributes to neuroendocrine control of female reproduction
Open accessAbstract
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.
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Female mice that over-express FGF21 are infertile.
“Female mice that over-express FGF21 are infertile, but whether this is a direct effect of FGF21 on fertility or rather a secondary consequence of FGF21-induced energy expenditure and relative caloric insufficiency has been disputed.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [100]
FGF21 has been shown to affect female reproduction.
“FGF21 has also been shown to affect female reproduction (100, 119).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [100]
FGF21 signals to the brain to suppress vasopressin-kisspeptin signaling, which impairs the proestrus surge in luteinizing hormone.
“One study found that FGF21 signals to the brain to suppress vasopressin–kisspeptin signaling, which impairs the proestrus surge in luteinizing hormone (100).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [100]
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- Authors
- Owen, B. M., Bookout, A. L., Ding, X., Lin, V. Y., Atkin, S. D., Gautron, L., Kliewer, S. A., & Mangelsdorf, D. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kliewer, Steven A
- Mangelsdorf, David J
- Venue
- Nature Medicine
- Published
- 2013-08-11
- Volume
- 19
- Issue
- 9
- Pages
- 1153-1156
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3769455
- OpenAlex
- W1963690531
- Cited by
- 230
- References
- 30
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 11 · 2023: 17 · 2022: 10 · 2021: 17 · 2020: 20 · 2019: 21 · 2018: 18 · 2017: 16 · 2016: 24 · 2015: 24 · 2014: 19 · 2013: 6
- FWCI
- 29.48
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (T32GM007062, GM007062, RL1GM084436)
- National Institute of Diabetes and Digestive and Kidney Diseases (U19 DK-62434, U19DK062434, R56DK089600, R01DK067158)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD028934, U54-HD-28934)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- FGF21, female reproduction, suprachiasmatic nucleus, neuroendocrine regulation, nutritional deficiency, luteinizing hormone surge, β-Klotho, hepatokines, liver-brain axis, circadian rhythm
- MeSH terms
- Klotho Proteins, Animals, Energy Metabolism, Female, Fibroblast Growth Factors, Hypothalamus, Infertility, Female, Luteinizing Hormone, Membrane Proteins, Mice, Inbred C57BL, Proestrus, Reproduction, Starvation, Suprachiasmatic Nucleus, Vasopressins, Signal Transduction, Mice, Knockout, Mice, Kisspeptins
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