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An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells. Am J Physiol Regul Integr Comp Physiol 2003 Jun;284(6):R1631-5

Date

04/12/2003

Pubmed ID

12689852

DOI

10.1152/ajpregu.00753.2002

Scopus ID

2-s2.0-0038515409   11 Citations

Abstract

Oxidized derivatives of linoleic acid have the potential to alter steroidogenesis. One such derivative is 12,13-epoxy-9- keto-10-(trans)-octadecenoic acid (EKODE). To evaluate the effect of EKODE on corticosterone production, dispersed rat zona fasciculata/reticularis (subcapsular) cells were incubated for 2 h with EKODE alone or together with rat ACTH (0, 0.2, or 2.0 ng/ml). In the absence of ACTH, EKODE (26 microM) increased corticosterone production from 5.3 +/- 2.3 to 14.7 +/- 5.0 ng. 10(6) cells. h(-1). The stimulatory effect of ACTH was increased threefold in the presence of EKODE (26.0 microM). Cholesterol transport/P-450scc activity was assessed by measuring basal and cAMP-stimulated pregnenolone production in the presence of cyanoketone (1.1 microM). EKODE (13.1 and 26.0 microM) significantly increased basal and cAMP-stimulated (0.1 mM) pregnenolone production. In contrast, EKODE decreased the effect of 1.0 mM cAMP. EKODE had no effect on early or late-pathway activity in isolated mitochondria. We conclude that EKODE stimulates corticosterone biosynthesis and amplifies the effect of ACTH. Increased levels of fatty acid metabolites may be involved in the increased glucocorticoid production observed in obese humans.

Author List

Bruder ED, Ball DL, Goodfriend TL, Raff H

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

Adrenal Glands
Adrenocorticotropic Hormone
Animals
Corticosterone
Dose-Response Relationship, Drug
Linoleic Acid
Male
Oleic Acids
Oxidation-Reduction
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d