title: Orexin A-mediated stimulation of 3β-HSD expression and testosterone production through MAPK signaling pathways in primary rat Leydig cells.
abstract: BACKGROUND
  Orexin A (ORA) regulates food intake, energy metabolism, gastrointestinal and reproductive functions.
  
  
  OBJECTIVE
  The purpose of this study was to demonstrate whether the expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and testosterone was stimulated by ORA and mediated through mitogen-activated protein kinases (MAPK) in rat Leydig cells.
  
  
  METHODS
  Primary Leydig cells were isolated from male rat testes, cultured, and treated with ORA under various conditions.
  
  
  RESULTS
  Orexin receptor 1 (OX (1) R) mRNA, but not orexin receptor 2 mRNA, was detected in primary Leydig cells. ORA up-regulated the expression of OX( 1) R mRNA and protein in a dose-responsive manner and increased the phosphorylation of extracellular receptor kinase 1/2 (ERK1/2) and p38 MAPK levels, but did not affect the phosphorylation of the JNK MAPK. Phosphorylation of ERK1/2 and p38 MAPKs by ORA was blocked with U0126 and SB203580 inhibitors, respectively. An OX(1)R-specific inhibitor, SB334867, also blocked the phosphorylation of ERK1/2 and p38 by ORA. Inhibitor treatment also blocked 3β-HSD expression and testosterone production.
  
  
  CONCLUSIONS
  These results demonstrate that ORA activation of OX(1)R up-regulates 3β-HSD expression and testosterone production via the ERK1/2 and p38 MAPKs signaling pathways in primary rat Leydig cells.
authors: D
authors: D
authors: Zheng
authors: Y
authors: Y
authors: Zhao
authors: Y
authors: Y
authors: Shen
authors: X
authors: X
authors: Chang
authors: S
authors: S
authors: Ju
authors: L
authors: L
authors: Guo
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D064446:Orexin Receptors / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D012333:RNA, Messenger; D013739:Testosterone; D015096:3-Hydroxysteroid Dehydrogenases; D020928:Mitogen-Activated Protein Kinases