ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P27

Modulation of adrenocortical aldosterone and cortisol synthesis by in vitro oxidized low density lipoprotein

Steffi Kopprasch1, Ishrath Ansurudeen1, Juergen Graessler1, Stefan R Bornstein1 & Jens Pietzsch1,2

1Department of Internal Medicine 3, CG Carus Medical School, Dresden, Germany; 2Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Dresden-Rossendorf, Germany.

Objectives: Oxidative stress is of critical importance in the pathogenesis of endocrinopathies. Since cholesterol serves as a major source of steroid hormone synthesis we investigated the effect of hypochlorite-modified low density lipoprotein (LDL) on aldosterone and cortisol release from human adrenocortical NCI-H295R cells.

Methods: Native LDL obtained from healthy volunteers was oxidized to varying degrees by sodium hypochlorite. The resulting modified LDL was biochemically characterized by gas chromatography–mass spectrometry (GC–MS) analysis. Human NCI-H295R cells were cultured in DMEM/F12. Aldosterone release in supernatants was measured by RIA and cortisol secretion was determined by competitive luminometric assay.

Results: Incubation of LDL with sodium hypochlorite resulted in increasing concentrations of the apolipoprotein B-100 oxidation markers HAVA, HACA, and 3-chlorotyrosine in dependence on the degree of oxidation. Incubation of adrenocortical cells with 10–100 μg/ml native or oxidized LDL for 24 h stimulated hormone release dose-dependently up to 3-fold. Subsequent stimulation of NCI-H295R cells with the physiological stimulus angiotensin II induced an additional hormone secretion up to 2.9-fold in LDL-pretreated samples. Compared to native LDL, oxidized LDL induced a smaller stimulation of hormone secretion that decreased with increasing degree of oxidation.

Conclusion: Oxidation of LDL may contribute to endocrine dysfunction by decreasing adrenocortical aldosterone and cortisol release.

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