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A naturally hypersensitive glucocorticoid receptor elicits a compensatory.pdf 915,04KB
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1000 Titel
  • A naturally hypersensitive glucocorticoid receptor elicits a compensatory reduction of hypothalamus–pituitary–adrenal axis activity early in ontogeny
1000 Autor/in
  1. Muráni, Eduard |
  2. Ponsuksili, Siriluck |
  3. Jaeger, Alexandra |
  4. Görres, Andreas |
  5. Tuchscherer, Armin |
  6. Wimmers, Klaus |
1000 Erscheinungsjahr 2016
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-07-20
1000 Erschienen in
1000 Quellenangabe
  • 6:150193
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • http://doi.org/10.1098/rsob.150193 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967818/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • We comprehensively characterized the effects of a unique natural gain-of-function mutation in the glucocorticoid receptor (GR), GRAla610Val, in domestic pigs to expand current knowledge of the phenotypic consequences of GR hypersensitivity. Cortisol levels were consistently reduced in one-week-old piglets, at weaning and in peripubertal age, probably due to a reduced adrenal capacity to produce glucocorticoids (GC), which was indicated by an adrenocortical thinning in GRAla610Val carriers. Adrenocorticotrophic hormone (ACTH) levels were significantly reduced in one-week-old piglets only. Expression analyses in peripubertal age revealed significant downregulation of hypothalamic expression of CRH and AVP, the latter only in females, and upregulation of hepatic expression of SERPINA6, by GRAla610Val. Transcriptional repression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) from GRAla610Val carriers was more sensitive to dexamethasone treatment ex vivo. However, no significant effects on growth, body composition, blood chemistry or cell counts were observed under baseline conditions. These results suggest that GRAla610Val-induced GR hypersensitivity elicits a compensatory reduction in endogenous, bioactive glucocorticoid levels via readjustment of the hypothalamus–pituitary–adrenal (HPA) axis early in ontogeny to maintain an adequate response, but carriers are more sensitive to exogenous GC. Therefore, GRAla610Val pigs represent a valuable animal model to explore GR-mediated mechanisms of HPA axis regulation and responses to glucocorticoid-based drugs.
1000 Sacherschließung
lokal molecular biology
lokal genetics
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/TXVyw6FuaSwgRWR1YXJk|https://frl.publisso.de/adhoc/creator/UG9uc3Vrc2lsaSwgU2lyaWx1Y2s=|https://frl.publisso.de/adhoc/creator/SmFlZ2VyLCBBbGV4YW5kcmE=|https://frl.publisso.de/adhoc/creator/R8O2cnJlcywgQW5kcmVhcw==|https://frl.publisso.de/adhoc/creator/VHVjaHNjaGVyZXIsIEFybWlu|http://orcid.org/0000-0002-9523-6790
1000 Förderer
  1. Federal Ministry of Education and Research |
  2. Leibniz Institute for Farm Animal Biology (FBN) |
  3. Leibniz Association |
1000 Fördernummer
  1. -
  2. -
  3. -
1000 Förderprogramm
  1. Phänomics network of competence
  2. -
  3. Open Access fund
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Federal Ministry of Education and Research |
    1000 Förderprogramm Phänomics network of competence
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Leibniz Institute for Farm Animal Biology (FBN) |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Leibniz Association |
    1000 Förderprogramm Open Access fund
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403724.rdf
1000 Erstellt am 2017-08-08T12:31:39.261+0200
1000 Erstellt von 122
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1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Tue Nov 27 14:47:13 CET 2018
1000 Objekt bearb. Tue Nov 27 14:47:13 CET 2018
1000 Vgl. frl:6403724
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403724 |
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1000 Sichtbarkeit Daten public
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