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% O 2, then transitioned them to 20% O 2 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.Conclusion:These data suggest that the hypoxic/normoxic transition at birth contributes to perinatal changes in adrenal steroidogenesis.