title: Steroidogenesis in aldosterone-producing adenoma revisited by transcriptome analysis.
abstract: BACKGROUND
  Primary aldosteronism (PAL) is the most frequent cause of secondary arterial hypertension. In PAL, aldosterone production is chronic, excessive, and autonomous.
  
  
  OBJECTIVE
  The objective of this study was to identify the angiotensin-II independent alterations of steroidogenesis responsible for PAL.
  
  
  METHODS
  Genomewide gene expression was compared in two tissues differentiated for aldosterone production, both nonstimulated by circulating angiotensin II and differing in their autonomy to produce aldosterone: aldosterone-producing adenoma (APA) and its adjacent dissected zona glomerulosa (ZG).
  
  
  METHODS
  The setting of this study was the Comete Network.
  
  
  METHODS
  Patients with APA were studied.
  
  
  METHODS
  Transcriptome comparison was made of one APA and its adjacent ZG by serial analysis of gene expression; validation by in situ hybridization was performed for 19 genes in 11 samples.
  
  
  RESULTS
  The study outcome was genes differentially expressed in APA and adjacent ZG.
  
  
  RESULTS
  Activation of steroidogenesis in PAL is restricted to the overexpression of the enzymes producing aldosterone-specific steroids, aldosterone synthase and also 21-hydroxylase, suggesting that upstream precursor production is not limiting. Increased expression of high-density lipoprotein receptor, adrenodoxin and P450 oxidoreductase suggests that these systems provide cholesterol and electrons to the mitochondrial steroidogenic enzymes. As for acute stimulation of aldosterone production, an activation of calcium signaling is suggested by concordant overexpression of calcium-binding proteins or effectors. Calcium activation may result from an abnormal activity of G(q) protein-coupled receptors. This calcium activation may be the starting point of the other gene expression changes observed in APA. Finally, other differentially expressed genes include three genes encoding unidentified proteins.
  
  
  CONCLUSIONS
  This work provides an original and integrated view of the mechanisms of aldosterone production in PAL.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique 8104, Université Paris 5, Institut Cochin, 24 rue du Fg Saint Jacques, 75014 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Assié
authors.forename: Colette
authors.initials: C
authors.lastname: Auzan
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gasc
authors.forename: Erno
authors.initials: E
authors.lastname: Baviera
authors.forename: André
authors.initials: A
authors.lastname: Balaton
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Elalouf
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Eric
authors.initials: E
authors.lastname: Clauser
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004583:Electrons; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000096:biosynthesis*; D014158:Transcription, Genetic; D015384:Zona Glomerulosa / Q000378:metabolism
chemical_list: D013256:Steroids; D000450:Aldosterone; D002784:Cholesterol; D002118:Calcium