Endocrine Abstracts

JOINT2740

Background: Phthalates entail as endocrine disrupting chemicals and have been shown to be associated with a range of endocrine and metabolic disorders. Dibutylphthalate (DBP) and Diethylhexylphthalate (DEHP) account as one of the most common used phthalates and are found in everyday products, toys and medical equipment. In humans they are quickly metabolized to monobutylphthalate (MBP) and monoethylhexylphthalate (MEHP). We investigated the influence of those two metabolites on cultured adrenocortical cells In vitro.

Methods: We exposed cultured HAC15 cells to five different concentrations (ranging from 1nM to 10µM) of MBP, MEHP and the mixture of both, and assessed cell viability, expression levels of key enzymes of steroidogenesis and levels of reactive oxygen species (ROS).

Results: Cell viability was significantly decreased upon exposure of high concentrations of MBP (10µM), while it was increased upon exposure of medium concentrations (100nM) of MEHP. qRT-PCR analysis revealed a significant decrease of mRNA expression of CYP11B2 upon exposure of even low MBP concentrations (P = 0. 0002) while MEHP disrupted CYP11B2 expression in a non-monotonic manner (P < 0. 0001). Expression levels of CYP11B1 and CYP21A2 were decreased upon exposure of high concentrations of both chemicals. The results of co-exposure of both phthalates demonstrated an additive effect on CYP11B2 and CYP11B1 expression, while expression of CYP21A2 was increased. There was an increase of ROS by 20% upon exposure of phthalate mixture (P < 0. 05).

Conclusion: The data suggest that even low concentrations of MBP and MEHP can cause serious disruption of adrenal corticosteroid synthesis, which is even intensified upon co-exposure of both and potentially mediated by increased ROS. Further studies are required to study the influence upon co-exposure with angiotensin II and ACTH as well as the underlying mechanism.