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DOI: 10.1055/s-2006-956182
© Georg Thieme Verlag KG Stuttgart · New York
An Oxidized Derivative of Linoleic Acid Stimulates Dehydroepiandrosterone Production by Human Adrenal Cells
Publication History
Received 12 May 2006
Accepted after revision 26 July 2006
Publication Date:
12 December 2006 (online)
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Abstract
We previously reported that an oxidized derivative of linoleic acid stimulated steroidogenesis in rat adrenal cells. This derivative was also detected in human plasma, and was positively correlated with visceral adiposity and plasma DHEA-S. The present study sought to characterize the effects of this derivative, 12,13-epoxy-9-keto-(10-trans)-octadecenoic acid (EKODE), on steroid production by normal human adrenocortical cells obtained during clinically-indicated adrenalectomy. Cell suspensions were incubated in the presence of varying concentrations of EKODE and ACTH. EKODE (16 μM) significantly increased DHEA production by 28% under basal conditions and by 25% in the presence of a low concentration of ACTH (0.2 ng/ml). The effect on DHEA was absent at a higher ACTH concentration (2.0 ng/ml). EKODE decreased cortisol production by 16% (low ACTH) and 25% (high ACTH), but was without effect on cortisol under basal conditions. The results suggest that EKODE affects adrenal DHEA production in the human, possibly by modulating steroidogenic enzyme activity. We postulate that excess visceral fat delivers fatty acids to the liver, where oxidized derivatives are formed that modulate adrenal steroidogenesis. This may be an important phenomenon in the genesis of changes in adrenal function associated with syndromes of obesity, especially those that include androgen excess.
Key words
Adrenal cortex - steroidogenesis - androgens - fatty acids
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Correspondence
H. RaffPh.D.
Endocrinology Aurora St. Luke's Physician's Office Building
2801 W. KK River Pky
Suite 245
Milwaukee WI 53215
Phone: +1/414/649 64 11
Fax: +1/414/649 57 47
Email: hraff@mcw.edu