title: Glucocorticoid treatment is associated with decreased expression of processed AVP but not of proAVP, neurophysin or oxytocin in the human hypothalamus: are PC1 and PC2 involved?
abstract: OBJECTIVE
  We reported earlier that vasopressin (AVP) peptide expression is significantly decreased in the postmortem hypothalamus of glucocorticoid (GC) treated patients, while such a decrease was not observed in AVP prohormone (proAVP) expression. This indicated a GC-induced suppression of AVP synthesis at the posttranslational level. Here, we investigated in detail whether this decreased levels of AVP expression in GC treated patients might be due to the down regulation of the prohormone convertases PC-1 and PC-2, and the molecular chaperone 7B2, as was reported previously in some AVP-related disorders.
  
  
  METHODS
  An immunocytochemical study was performed on post-mortem hypothalami of GC exposed patients and controls, in which quantification of proAVP, AVP, neurophysin (NP) and oxytocin (OXT) expression were done along with the quantification of PC1, PC2 and 7B2 expression in the paraventricular nucleus, by using a computerized image analysis system.
  
  
  RESULTS
  Expression of processed AVP in GC exposed patients was significantly decreased (p=0.021), while the amount of proAVP expression was unchanged. Despite the strong correlation between AVP and NP (the other cleavage product of proAVP) expression in the GC group (r=0.917, p=0.004), the mean NP immunoreactivity did not show a significant decrease in this group. Also the OXT expression was similar in both groups. Although in most of the GC treated patients, the expression intensities of PC1 and PC2 were decreased parallel to the decrease in AVP, the mean expression levels of neither of PC1 and PC2, nor of 7B2 were statistically different between the groups (p=0.20-0.80).
  
  
  CONCLUSIONS
  We conclude that the suppression of AVP expression by GCs is not mediated solely by the down regulation of PC1, PC2 or 7B2. Other mechanisms, which may contribute to the GC-induced posttranslational suppression of AVP, are discussed.
authors.affiliation: Netherlands Institute for Brain Research, Meibergdreef 33 1105 AZ Amsterdam, The Netherlands.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Erkut
authors.forename: B A Th F
authors.initials: BA
authors.lastname: Gabreëls
authors.forename: J
authors.initials: J
authors.lastname: Eikelenboom
authors.forename: F W
authors.initials: FW
authors.lastname: van Leeuwen
authors.forename: D F
authors.initials: DF
authors.lastname: Swaab
mesh_terms: D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051859:Neuroendocrine Secretory Protein 7B2; D009481:Neurophysins / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D013381:Subtilisins / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009481:Neurophysins; D010907:Pituitary Hormones; C497678:SCG5 protein, human; C453701:proAVP hormone; D014667:Vasopressins; D001127:Arginine Vasopressin; D010121:Oxytocin; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases