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Hypoxia in vivo inhibits aldosterone synthesis and aldosterone synthase mRNA in rats. J Appl Physiol (1985) 1996 Aug;81(2):604-10

Date

08/01/1996

Pubmed ID

8872624

DOI

10.1152/jappl.1996.81.2.604

Scopus ID

2-s2.0-0029750202   32 Citations

Abstract

Hypoxia leads to a decrease in aldosterone that 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 P-450c11AS 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 P-450c11AS) without a change in the other mitochondrial cytochrome P-450 enzyme activities. Adrenal cells from rats exposed to hypoxia also demonstrated a three- to fourfold decrease in P-450c11AS mRNA without a change in the other mitochondrial cytochrome P-450 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 (P-450c11AS).

Author List

Raff H, Jankowski BM, Engeland WC, Oaks MK

Author

Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aldosterone
Animals
Cytochrome P-450 CYP11B2
Cytochrome P-450 Enzyme System
DNA Primers
Histocytochemistry
Hypoxia
In Situ Hybridization
In Vitro Techniques
Male
Polymerase Chain Reaction
RNA, Messenger
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d