MON-035 Aldosterone Secretion in a Human Adrenal Cell Line Is Enhanced by the Endocrine-Disrupting Chemical Di-(2-Ethylhexyl) Phthalate (DEHP)

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine-disrupting chemical that is widely used as a plasticizer in the production of polyvinyl chloride containing plastics. DEHP is a component of many common household items (toys, packaging, furniture, etc.) and medical devices, resulting in significant and chronic human exposure. Human exposure to DEHP has been linked to androgen disruption and developmental toxicity, including cryptorchidism, decreased anogenital distance, and decreased testosterone levels. Other adrenal corticosteroids are also susceptible to the endocrine-disrupting effects of DEHP. One study has demonstrated that fetal exposure to DEHP results in altered adrenal aldosterone production in adult rats. Due to these potential effects of DEHP on adrenal cortex steroidogenesis, the focus of our studies is to characterize the effect of DEHP on aldosterone secretion in a human adrenocortical cell line. HAC15 cells were exposed to vehicle or various concentrations of DEHP (10 nM-30 μM). After 72 h, cell viability, aldosterone secretion, and gene expression of enzymes and cofactors involved in aldosterone synthesis was examined. No effects on cell viability were observed with the concentrations studied. Basal aldosterone secretion was significantly increased from 100 nM-30 μM DEHP, with maximal secretion at 10 μM (in pg/mL: vehicle, 75.6±3.5; 10 μM DEHP, 7735.2±151.3; n=8). Ang II-stimulated aldosterone secretion was significantly increased from 100 nM-30 μM DEHP, with maximal secretion at 10 μM (in pg/mL: vehicle, 4278.9±110.2; 10 μM DEHP, 18651.7±572.2; n=8). ACTH-stimulated aldosterone secretion was significantly increased from 100 nM-30 μM DEHP, with maximal secretion at 10 μM (in pg/mL: vehicle, 124.0±3.7; 10 μM DEHP, 23455.8±272.7; n=8). Gene expression of most enzymes and cofactors involved in aldosterone synthesis were increased by 10 μM DEHP. Aldosterone synthase (CYP11B2) had the greatest induction at 175.2±2.0 fold. These data support the evidence that DEHP disrupts the regulation of aldosterone secretion and provides further evidence that DEHP is an endocrine disruptor.