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1 Endocrine Research Laboratory, St. Luke's Medical Center, Milwaukee 53215; 2 Departments of Medicine and Pharmacology, William S. Middleton Memorial Veterans Hospital and University of Wisconsin, Madison 53705; and 3 Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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 µM) increased
corticosterone production from 5.3 ± 2.3 to 14.7 ± 5.0 ng · 106 cells · h
1. The
stimulatory effect of ACTH was increased threefold in the presence of
EKODE (26.0 µM). Cholesterol transport/P-450scc activity was assessed by measuring basal and cAMP-stimulated pregnenolone production in the presence of cyanoketone (1.1 µM). EKODE (13.1 and
26.0 µM) 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.
steroidogenesis; glucocorticoid; fatty acid; zona fasciculata; epoxide
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