Endocrine Abstracts

Background: Bisphenol A (BPA) is known to act as an endocrine disruptor in different organs. However, its impact on adrenal gland functionality is largely unknown. This also applies to its substitute substances bisphenol F (BPF) and S (BPS). Therefore, experiments addressing this subject are urgently needed.Methods: The human adrenocortical cell lines NCI-H295R and MUC-1 were treated with increasing concentrations (1 nM – 1 mM) o...

Background: The diagnostic workup of primary aldosteronism (PA) is challenging and the current screening tool, aldosterone-renin ratio, is increasingly challenged. Due to interference with immunoassays and the general high variability of plasma aldosterone levels false-positive as well as false-negative results are probably more frequent than previously assumed. Therefore, we aimed at the establishment of a reliable LC-MS/MS method to analyze aldosterone and related steroids i...

Background: Bisphenol A (BPA) acts as an endocrine disruptor in different endocrine systmes. However, its impact on the adrenal cortex and steroidogenesis is largely unknown. This also applies to its substitute substances bisphenol F (BPF) and S (BPS). Therefore, experiments addressing this subject are urgently needed.Methods: The human adrenocortical cell lines NCI-H295R and MUC-1 were treated with increasing concentrations (1 nM–1 mM) of bisphenol...

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). We have found that mitotane leads to endoplasmic reticulum stress and decreased viability in ACC cells. It is not known by which downstream mechanisms cell death is induced by mitotane.Aim: To characterize the mechanisms underlying cell death resulting from mitotane treatment in ACC cells.Methods: Lipid peroxidation in the ACC cell line ...

Background: Mitotane is the only approved treatment for advanced adrenocortical carcinoma and was shown to inhibit Sterol-O-Acyl transferase 1 (SOAT1) which leads to the depletion of cholesterol esters and increase of free cholesterol in the ACC cell line H295R. Downstream activation of the endoplasmic reticulum stress (ER-stress) pathway results in decreased adrenocortical cell viability.Aim: To better characterize the effects of SOAT1 inhibition in ACC...

Objective: The saline infusion test (SIT) is a standard confirmatory test for primary aldosteronism (PA) and based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Due to the more widespread use of liquid chromatography tandem mass spectrometry (LC-MS/MS) in clinical routine, we aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the d...

Background: The human cytochrome P450 (CYP) 2W1 is involved in the metabolism of several endogenous substrates, including lysophospholipids and fatty acids. Using a polyclonal antibody, we previously demonstrated a high CYP2W1 immunoreactivity in adrenocortical tumors, particularly in those secreting steroids. The aim of the study was to better elucidate the relationship between CYP2W1 and steroid secretion in adrenocortical carcinoma (ACC) H295R cell line and in a larger seri...

Context: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC) and in clinical use for more than 50 years. Mitotane counteracts both tumour growth and tumoral steroid hormone production but treatment is associated with severe side effects. The molecular mechanism of mitotane is still unknown, which hampers progress in treatment of ACC.Objective: To identify the mechanism of action and molecular target of mitotane.<p class...