CRH and SRIF have opposite effects on the Wnt/β-catenin signalling pathway through PKA/GSK-3β in corticotroph pituitary cells.
The Wnt/ß-catenin signalling pathway is involved in tumorigenesis including endocrine tumors. We investigated the Wnt/ß-catenin pathway's modulation by corticotropin-releasing hormone (CRH) and somatostatin or somatotropin release-inhibiting factor (SRIF) in mouse pituitary AtT-20 corticotroph cells. The Wnt/β-catenin signalling pathway was activated by CRH and inhibited by SRIF. We provide evidence that cAMP/PKA signalling is involved affecting the GSK-3β phosphorylation status at phospho-GSK-3β (Ser9), thereby altering β-catenin degradation downstream. Furthermore, CRH and SRIF showed concordant effects on cell proliferation. Our data demonstrate an important role of the Wnt/β-catenin pathway in the proliferative control of pituitary corticotroph cells and describe a mechanism for its regulation by CRH and SRIF.
Khattak
Muhammad Nasir Khan
MN
Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany.
Buchfelder
Michael
M
Kleindienst
Andrea
A
Schöfl
Christof
C
Kremenevskaja
Natalia
N
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000502:physiology; D051153:Wnt Proteins / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C090743:Tcf4 protein, mouse; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3