title: Potential role of increased oxygenation in altering perinatal adrenal steroidogenesis.
abstract: BACKGROUND
  At birth, the large fetal adrenal involutes rapidly, and the patterns of steroidogenesis change dramatically; the event(s) triggering these changes remain largely unexplored. Fetal abdominal viscera receive hypoxic blood having a partial pressure of oxygen of only ~2 kPa (20-23 mm Hg); perinatal circulatory changes change this to adult values (~20 kPa). We hypothesized that transition from fetal hypoxia to postnatal normoxia participates in altering perinatal steroidogenesis.
  
  
  METHODS
  We grew midgestation human fetal adrenal cells and human NCI-H295A adrenocortical carcinoma cells in 2% O2, then transitioned them to 20% O2 and quantitated steroidogenic mRNAs by quantitative PCR and microarrays.
  
  
  RESULTS
  Transitioning fetal adrenal cells from hypoxia to normoxia increased mRNAs for 17α-hydroxylase/17,20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD2), and steroidogenic acute regulatory protein (StAR). We repeated the protocol with NCI-H295A cells acclimated to hypoxia for 15 d, quantitating 31,255 transcripts by microarray. Using an arbitrary 1.5-fold difference, 1 d of normoxia increased 4 transcripts and decreased 56, whereas 2 d of normoxia increased 62 transcripts and decreased 105. P450c17, 3βHSD2, and StAR were ranked among the top eight increased transcripts.
  
  
  CONCLUSIONS
  These data suggest that the hypoxic/normoxic transition at birth contributes to perinatal changes in adrenal steroidogenesis.
authors.affiliation: Department of Pediatrics, University of California-San Francisco, San Francisco, California.
authors.forename: Vishal
authors.initials: V
authors.lastname: Agrawal
authors.affiliation: Department of Pediatrics, University of California-San Francisco, San Francisco, California.
authors.forename: Meng Kian
authors.initials: MK
authors.lastname: Tee
authors.affiliation: Department of Pediatrics, University of California-San Francisco, San Francisco, California.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: 1] Blood Systems Research Institute, University of California-San Francisco, San Francisco, California [2] Department of Laboratory Medicine, University of California-San Francisco, San Francisco, California.
authors.forename: Marcus O
authors.identifier: 0000000189466605
authors.initials: MO
authors.lastname: Muench
authors.affiliation: Department of Pediatrics, University of California-San Francisco, San Francisco, California.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000311:Adrenal Glands / Q000254:growth & development* / Q000378:metabolism*; D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry*; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D046228:Microarray Analysis; D010100:Oxygen / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D003470:Culture Media; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D015096:3-Hydroxysteroid Dehydrogenases; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D010100:Oxygen