title: Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis.
abstract: OBJECTIVE
  Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin/glucagons/vasoactive intestinal peptide family, induces the expression of catecholamine-synthesizing enzymes in adrenal medullary cells. In addition, PACAP and its receptor have been detected in human pheochromocytoma tissues, though it is not yet known whether PACAP enhances the expression of genes encoding catecholamine-synthesizing enzymes. To address this question, we analyzed PACAP, PACAP receptor, and tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) mRNAs in pheochromocytomas.
  
  
  METHODS
  The levels of the mRNA for PACAP and vasoactive intestinal peptide (VIP), and their receptors, and for TH and PNMT were measured by RT-PCR or real-time PCR analysis, and the concentrations of catecholamines were measured by HPLC in 24 intra-adrenal and six extra-adrenal pheochromocytomas.
  
  
  RESULTS
  mRNA expression of PACAP and its receptor VPAC1R were detected in many pheochromocytomas (24/30 and 29/30, respectively), but mRNA expression of the PAC1R and VPAC2R receptor subtypes were detected in only one of six extra-adrenal pheochromocytomas. PACAP mRNA expression correlated with TH (p=0.0018) and PNMT (p=0.05) mRNA expression, as well as epinephrine (p=0.0342) levels in 16 intra-adrenal pheochromocytomas.
  
  
  CONCLUSIONS
  Our findings support a possible role for PACAP in the regulation of expression of genes encoding catecholamine-synthesizing enzymes in intra-adrenal pheochromocytomas.
authors.affiliation: Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. k_isobe@md.tsukuba.ac.jp
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Isobe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Toru
authors.initials: T
authors.lastname: Yashiro
authors.forename: Toru
authors.initials: T
authors.lastname: Nanmoku
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takekoshi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakai
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009479:Neuropeptides / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495401:ADCYAP1 protein, human; C495503:ADCYAP1R1 protein, human; D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone