Roelofs, Maarke J E van den Berg, Martin Bovee, Toine F H Piersma, Aldert H van Duursen, Majorie B MĪlthough much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile is lacking. Structural bisphenol analogues differentially target steroidogenesis in murine MA- 10 Leydig cells as well as the glucocorticoid receptor.

These results indicate that MEHP inhibits MA- 10 Leydig cell steroidogenesis by targeting LH-stimulated cAMP production and cholesterol transport, and that a likely mechanism by which MEHP acts is through increased oxidative stress. In cells in which intracellular glutathione was depleted by buthionine sulfoximine pretreatment, the increases in ROS and decreases in progesterone in response to MEHP treatment were exacerbated. Increased levels of reactive oxygen species (ROS) occurred in response to MEHP. Incubation of MEHP-treated cells with dibutyryl-cAMP, 22-hydroxycholesterol or pregnenolone inhibited the reductions in progesterone. cAMP did not decrease in response to MEHP when the cells were incubated with cholera toxin or forskolin. We show that incubating MA- 10 Leydig cells with mono-(2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone (LH)-stimulated cAMP and progesterone productions. However, the affected components of the steroidogenic pathway, and the mechanisms involved, remain uncertain. Previous studies have shown that phthalate exposure can suppress steroidogenesis. Lin, Chieh-Yin Liu, June Traore, Kassim Papadopoulos, Vassilios Zirkin, Barry R. Oxidative Stress and Phthalate-Induced Down-Regulation of Steroidogenesis in MA- 10 Leydig Cells*

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