Hypoxia in vivo inhibits aldosterone synthesis and aldosterone
synthase mrna in the rat.
Raff, Hershel, Barbara M. Jankowski, William C. Engeland, and Martin
K. Oaks.
Endocrine and Immunology Research Laboratories (HR, BMJ, MKO), St.
Luke's Medical Center, Medical College of Wisconsin, Milwaukee, WI
53215 and Department of Surgery, University of Minnesota Medical
School, Minneapolis, MN 55455
APStracts 3:0135A, 1996.
Hypoxia leads to a decrease in aldosterone which cannot be entirely
explained by extrinsic controllers of adrenal function. We have shown
that acute hypoxia attenuates aldosterone synthesis via a direct
inhibition of the function of the aldosterone enzyme pathway. The
mechanism of the sustained decrease in aldosterone during chronic
hypoxia is unknown. The present study evaluated the hypothesis that
chronic hypoxia leads to a decrease in the expression of the
steroidogenic enzyme P450c11AS unique to the aldosterone pathway.
Rats were exposed to 3 days of normoxia, moderate hypoxia (12% O2),
or severe hypoxia (10% O2). Adrenal glands were removed and prepared
for biochemical analysis of steroidogenesis in vitro (dispersed
capsular cells) and for measurement of steady state enzyme mRNA
levels by reverse transcription-competitive polymerase chain reaction
(RT-cPCR) and by in situ hybridization histochemistry (ISHH).
Moderate hypoxia had no effect on steroidogenesis. Adrenal cells from
rats exposed to severe hypoxia demonstrated a decreased conversion of
corticosterone to aldosterone (late pathway catalyzed by P450c11AS)
without a change in the other mitochondrial cytochrome P450 enzyme
activities. Adrenal cells from rats exposed to hypoxia also
demonstrated a 3-4 fold decrease in P450c11AS mRNA without a change
in the other mitochondrial cytochrome P450 enzymes mRNAs as
determined by either RT-cPCR or ISHH. We conclude that relatively
short term chronic hypoxia in rats leads to a decrease in
aldosteronogenesis by decreasing the expression of the gene for the
late pathway enzyme unique to the aldosterone pathway (P450c11AS).
Received 17 November 1995; accepted in final form 28 February
1996.
APS Manuscript Number A1206-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96