OXIDIZED PRODUCTS OF LINOLEIC ACID STIMULATE ADRENAL STEROIDOGENESIS

Abstract

Adrenal steroidogenesis is under complex control, and clinical observations suggest that not all regulators have been identified. We postulated that fatty acid oxidation products found in the diet or formed in the body could affect steroidogenesis. Linoleic acid is a prominent constituent of animal fat and is readily oxidized. We found that several products of linoleic acid oxidation affect production of aldosterone and corticosterone by isolated cells from rat adrenals. We characterized one linoleic acid derivative by gas chromatography/mass spectrometry. It is 12,13-epoxy-9-oxo-10(trans)-octadecenoic acid (“EKODE”). At concentrations between 1 and 30 µM, EKODE stimulated production of aldosterone by zona glomerulosa cells, but at concentrations above 50 µM, it was inhibitory. In zona fasciculata cells, EKODE stimulated corticosterone production at concentrations of 5 µM or greater, and there was no evidence of inhibition at high concentrations. Stimulation of steroidogenesis was observed after 15 min of incubation and continued for at least 2 hrs. The potential relevance of our findings to the hypertension of obesity is discussed.

ACKNOWLEDGMENTS

This work was supported in part by the U.S. Department of Veterans Affairs and the American Heart Association (T.G.) and grant NIH/DK54685 (H.R.).