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AMP-activated prote...
AMP-activated protein kinase (AMPK) signaling in GnRH neurons links energy status and reproduction.
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Franssen, D (författare)
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Barroso, A (författare)
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Ruiz-Pino, F (författare)
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Vázquez, M J (författare)
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García-Galiano, D (författare)
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Castellano, J M (författare)
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Onieva, R (författare)
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Ruiz-Cruz, M (författare)
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- Poutanen, Matti (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Gaytán, F (författare)
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Diéguez, C (författare)
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Pinilla, L (författare)
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Lopez, M (författare)
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Roa, J (författare)
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Tena-Sempere, M (författare)
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(creator_code:org_t)
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- 2021
- 2021
- Engelska.
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Ingår i: Metabolism: clinical and experimental. - 1532-8600. ; 115
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Reproduction is tightly coupled to body energy and metabolic status. GnRH neurons, master elements and final output pathway for the brain control of reproduction, directly or indirectly receive and integrate multiple metabolic cues to regulate reproductive function. Yet, the molecular underpinnings of such phenomenon remain largely unfolded. AMP-activated protein kinase (AMPK), the fundamental cellular sensor that becomes activated in conditions of energy deficit, has been recently shown to participate in the control of Kiss1 neurons, essential gatekeepers of the reproductive axis, by driving an inhibitory valence in situations of energy scarcity at puberty. However, the contribution of AMPK signaling specifically in GnRH neurons to the metabolic control of reproduction remains unknown.Double immunohistochemistry (IHC) was applied to evaluate expression of active (phosphorylated) AMPK in GnRH neurons and a novel mouse line, named GAMKO, with conditional ablation of the AMPK α1 subunit in GnRH neurons, was generated. GAMKO mice of both sexes were subjected to reproductive characterization, with attention to puberty and gonadotropic responses to kisspeptin and metabolic stress.A vast majority (>95%) of GnRH neurons co-expressed pAMPK. Female (but not male) GAMKO mice displayed earlier puberty onset and exaggerated LH (as surrogate marker of GnRH) responses to kisspeptin-10 at the prepubertal age. In adulthood, GAMKO females retained increased LH responsiveness to kisspeptin and showed partial resilience to the inhibitory effects of conditions of negative energy balance on the gonadotropic axis. The modulatory role of AMPK in GnRH neurons required preserved ovarian function, since the differences in LH pulsatility detected between GAMKO and control mice subjected to fasting were abolished in ovariectomized animals.Altogether, our data document a sex-biased, physiological role of AMPK signaling in GnRH neurons, as molecular conduit of the inhibitory actions of conditions of energy deficit on the female reproductive axis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- AMP-Activated Protein Kinases
- genetics
- metabolism
- Animals
- Energy Metabolism
- physiology
- Estrous Cycle
- metabolism
- Female
- Gonadotropin-Releasing Hormone
- metabolism
- Kisspeptins
- pharmacology
- Luteinizing Hormone
- blood
- Male
- Malnutrition
- metabolism
- Mice
- Mice
- Knockout
- Neurons
- drug effects
- metabolism
- Phosphorylation
- Reproduction
- physiology
- Sex Characteristics
- Signal Transduction
- drug effects
- physiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Franssen, D
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Barroso, A
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Ruiz-Pino, F
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Vázquez, M J
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García-Galiano, ...
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Castellano, J M
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visa fler...
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Onieva, R
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Ruiz-Cruz, M
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Poutanen, Matti
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Gaytán, F
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Diéguez, C
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Pinilla, L
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Lopez, M
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Roa, J
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Tena-Sempere, M
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
- Artiklar i publikationen
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Metabolism: clin ...
- Av lärosätet
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Göteborgs universitet