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O2 dependence of pregnenolone and aldosterone synthesis in mitochondria from bovine zona glomerulosa cells. J Appl Physiol (1985) 1995 May;78(5):1625-8

Date

05/01/1995

Pubmed ID

7649895

DOI

10.1152/jappl.1995.78.5.1625

Scopus ID

2-s2.0-0028989457   14 Citations

Abstract

Hypoxia in vivo results in a decrease in aldosterone not accounted for by extra-adrenal controllers. We have demonstrated that aldosteronogenesis but not cortisol synthesis in the whole cell is O2 sensitive. In the intact glomerulosa cell, this sensitivity is located in the late pathway step catalyzed by conversion of corticosterone to aldosterone (P-450aldo), whereas the early pathway catalyzed by conversion of cholesterol to pregnenolone (P-450scc) is not inhibited until PO2 is very low. Because P-450aldo and P-450scc are mitochondrial enzymes that depend on the same NADPH-specific electron transport proteins, we hypothesized that O2 sensitivity would be independent of energy production and expressed in isolated mitochondria. We measured the conversion of exogenous 25(OH)-cholesterol to pregnenolone and of exogenous corticosterone to aldosterone in the presence of cyanoketone in mitochondria isolated from bovine zona glomerulosa cells and exposed to an experimental gas (1-100% O2) vs. a room air control. Pregnenolone production was not affected until PO2 was < 35 Torr and decreased to almost nil when PO2 was < 30 Torr. In contrast, aldosterone production increased under hyperoxia and decreased under moderate decreases in O2. The conversion of corticosterone to aldosterone was maintained at approximately 50% of control, even when PO2 was < 20 Torr. The sensitivity of the aldosterone pathway to changes in O2 within the physiological range appears to reside in the mitochondrial late pathway (i.e., P-450aldo) and is not significantly influenced by cytosolic regulators of steroidogenesis or by limitation of reducing equivalents.

Author List

Raff H, Jankowski B

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
Cattle
Cholesterol
Corticosterone
Cytochrome P-450 Enzyme System
In Vitro Techniques
Mitochondria
Oxygen
Pregnenolone
Zona Glomerulosa
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