Corticotropin-releasing hormone stimulates SGK-1 kinase expression in cultured hippocampal neurons via CRH-R1

Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E938-46. doi: 10.1152/ajpendo.90462.2008. Epub 2008 Aug 19.

Abstract

Corticotropin-releasing hormone (CRH) has been shown to exhibit various functions in hippocampus. In the present study, we examined the effect of CRH on the expression of serum/glucocorticoid-inducible protein kinase-1 (SGK-1), a novel protein kinase, in primary cultured hippocampal neurons. A dose-dependent increase in mRNA and protein levels of SGK-1 as well as frequency of SGK-1-positive neurons occurred upon exposure to CRH (1 pmol/l to 10 nmol/l). These effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by the CRH-R2 antagonist astressin 2B. Blocking adenylate cyclase (AC) activity with SQ22536 and PKA with H89 completely prevented CRH-induced mRNA and protein expression of SGK-1. Blockage of PLC or PKC did not block CRH-induced SGK-1 expression. Our results suggest that CRH act on CRH-R1 to stimulate SGK-1 mRNA and protein expression in cultured hippocampal neurons via a mechanism that is involved in AC/PKA signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cells, Cultured
  • Corticotropin-Releasing Hormone / pharmacology*
  • Cyclic AMP / biosynthesis
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Antibody Technique
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / enzymology*
  • Immediate-Early Proteins / biosynthesis*
  • Immediate-Early Proteins / genetics
  • Neurons / drug effects
  • Neurons / enzymology*
  • Phospholipase C beta / antagonists & inhibitors
  • Phospholipase C beta / biosynthesis
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • RNA / biosynthesis
  • RNA / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / drug effects*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stimulation, Chemical

Substances

  • Enzyme Inhibitors
  • Immediate-Early Proteins
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • RNA
  • Corticotropin-Releasing Hormone
  • Cyclic AMP
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Phospholipase C beta