Transcriptional and metabolic effects of glucocorticoid receptor α and β signaling in zebrafish

Endocrinology
A ChatzopoulouMarcel J M Schaaf

Abstract

In humans and zebrafish, 2 glucocorticoid (GC) receptor (GR) splice variants exist: the canonical GR α-isoform (GRα), and the GRβ. In the present study, we have used the zebrafish model system in order to reveal genes affected by each of these 2 receptor isoforms. By injecting zebrafish embryos with different splice-blocking morpholinos, we could knock down both GR isoforms or could target the alternative splicing of the GR pre-mRNA in favor of the GRβ. In addition, specific GRβ overexpression was achieved by injecting mRNA. Embryos were treated with the synthetic GC dexamethasone, and transcriptome analysis was performed. Two distinct gene clusters were found that were regulated by GRα: one that was regulated by GRα under basal conditions (presence of endogenous cortisol only), and one that was regulated upon increased activation of GRα (using a pharmacological dose of dexamathasone). GRβ may act as a dominant-negative inhibitor of GRα when GRβ is overexpressed and the GRα expression level is knocked down simultaneously. However, without GRα knockdown, no evidence for this activity was found. In addition, the data indicate regulation of gene transcription through other mechanisms of action by GRβ. We also investigated the conc...Continue Reading

References

Jun 1, 1995·The Journal of Clinical Investigation·C M BambergerG P Chrousos
Jul 1, 1997·Physiological Reviews·S E Wendelaar Bonga
Mar 24, 1998·Molecular and Cellular Endocrinology·C M BambergerH M Schulte
May 15, 1998·Nature·J A Lefstin, K R Yamamoto
Feb 7, 2001·Trends in Endocrinology and Metabolism : TEM·J Carlstedt-Duke
Jun 30, 2000·Human Reproduction Update·M Beato, J Klug
May 22, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Claire GougatMarc Mathieu
Sep 13, 2002·American Journal of Physiology. Cell Physiology·Laura PujolsCésar Picado
Nov 21, 2002·Pharmacology & Therapeutics·Heike SchäckeKhusru Asadullah
Nov 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Inez RogatskyKeith R Yamamoto
Oct 19, 2004·Biochimica Et Biophysica Acta·Onard J L M SchoneveldWouter H Lamers
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jen-Chywan WangKeith R Yamamoto
May 14, 2005·Nature Reviews. Neuroscience·E Ron de KloetFlorian Holsboer
Aug 20, 2005·PLoS Genetics·Phillip Phuc LeKlaus H Kaestner
Oct 6, 2005·Science's STKE : Signal Transduction Knowledge Environment·George P Chrousos, Tomoshige Kino
Nov 24, 2005·Investigative Ophthalmology & Visual Science·Xinyu ZhangThomas Yorio
Jan 3, 2006·American Journal of Respiratory and Critical Care Medicine·Elena GolevaDonald Y M Leung
Jan 13, 2006·British Journal of Pharmacology·Julia C Buckingham
Aug 10, 2006·Stress : the International Journal on the Biology of Stress·O C Meijer
Jan 24, 2007·Molecular and Cellular Biology·Laura J Lewis-TuffinJohn A Cidlowski
Apr 19, 2007·Nature Reviews. Genetics·Graham J Lieschke, Peter D Currie
Jul 13, 2007·Molecular and Cellular Endocrinology·Alexandros Vegiopoulos, Stephan Herzig
Sep 13, 2007·The Journal of Biological Chemistry·Lijoy K MathewRobert L Tanguay
Nov 22, 2007·The Journal of Allergy and Clinical Immunology·Audrey KellyPaul Lavender
Dec 1, 2007·Reviews in Endocrine & Metabolic Disorders·Marjet D HeitzerDonald B DeFranco
Dec 22, 2007·Endocrinology·Marcel J M SchaafMichael K Richardson
Feb 19, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jedd M HillegassLori A White
Mar 18, 2008·Molecular Cell·Sam JohnGordon L Hager
Apr 16, 2008·European Journal of Pharmacology·Siem van der Laan, Onno C Meijer
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong ZhangTing Xi Liu
Oct 22, 2008·General and Comparative Endocrinology·Derek Alsop, Mathilakath Vijayan
Dec 20, 2008·Molecular Endocrinology·Karolien De Bosscher, Guy Haegeman
Jan 17, 2009·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Derek Alsop, Mathilakath M Vijayan
Jan 27, 2009·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·M J M SchaafH P Spaink
Mar 3, 2009·Biochemical and Biophysical Research Communications·Tomoshige KinoGeorge P Chrousos
Jun 27, 2009·The International Journal of Developmental Biology·Sebastiaan A BrittijnMichael K Richardson
Jul 28, 2009·Cellular and Molecular Life Sciences : CMLS·Tomoshige KinoGeorge P Chrousos
Oct 13, 2009·Steroids·Nicolas C NicolaidesEvangelia Charmandari
Nov 13, 2009·Annals of the New York Academy of Sciences·Javier R Revollo, John A Cidlowski
May 25, 2010·Steroids·Peter J SchoonheimMarcel J M Schaaf

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Citations

Sep 6, 2015·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Faiza SharifDanielle L Champagne
Jul 23, 2016·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Erin Faught, Mathilakath M Vijayan
Aug 25, 2016·BioMed Research International·Jing Ying HooBey Hing Goh
Dec 18, 2016·International Urology and Nephrology·Jieping Hu, Qingke Chen
Jul 9, 2016·The Journal of Endocrinology·K S WilsonM A Denvir
Apr 3, 2019·American Journal of Physiology. Endocrinology and Metabolism·Erin Faught, Mathilakath M Vijayan
May 25, 2016·Endocrinology·Antonia ChatzopoulouMarcel J M Schaaf
Dec 31, 2015·American Journal of Physiology. Endocrinology and Metabolism·Kezia JohnTerry D Hinds
Feb 11, 2020·Stress : the International Journal on the Biology of Stress·Konstantin A DeminAllan V Kalueff
May 10, 2020·BioMed Research International·Yuxiang HuangYongqiang Li
Mar 16, 2019·Frontiers in Cell and Developmental Biology·Thomas DickmeisPhilipp Gut
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Yufei XieMarcel J M Schaaf
Apr 24, 2019·Kidney International·Tilman Jobst-SchwanFriedhelm Hildebrandt
Apr 4, 2021·International Journal of Molecular Sciences·Patricia Ramos-Ramírez, Omar Tliba
Oct 13, 2020·General and Comparative Endocrinology·Karine RousseauSylvie Dufour

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