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


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

Kopprasch, S.; Ansurudeen, I.; Graessler, J.; Bornstein, S. R.; Pietzsch, J.

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.

  • Poster
    10th European Congress of Endocrinology, 03.-07.05.2008, Berlin, Deutschland
  • Abstract in refereed journal
    Endocrine Abstracts 16(2008), P27

Permalink: https://www.hzdr.de/publications/Publ-11401
Publ.-Id: 11401