Molecular Mechanisms Mediating the Effect of Mono-(2-ethylhexyl) Phthalate on Hormone-stimulated Steroidogenesis in MA-10 Mouse Tumor Leydig Cells

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2010 May 14

PMID 20463053

Citations 32

Authors

Jinjiang Fan

Kassim Traore

Wenping Li

Hakima Amri

Hongzhan Huang

Cathy Wu

Haolin Chen

Barry Zirkin

Vassilios Papadopoulos

Affiliations

Soon will be listed here.

Abstract

Di-(2-ethylhexyl) phthalate, a widely used plasticizer, and its active metabolite, mono-(2-ethylhexyl) phthalate (MEHP), have been shown to exert adverse effects on the reproductive tract in developing and adult animals. As yet, however, the molecular mechanisms by which they act are uncertain. In the present study, we address the molecular and cellular mechanisms underlying the effects of MEHP on basal and human chorionic gonadotropin (hCG)-stimulated steroid production by MA-10 Leydig cells, using a systems biology approach. MEHP induced dose-dependent decreases in hCG-stimulated steroid formation. Changes in mRNA and protein expression in cells treated with increasing concentrations of MEHP in the presence or absence of hCG were measured by gene microarray and protein high-throughput immunoblotting analyses, respectively. Expression profiling indicated that low concentrations of MEHP induced the expression of a number of genes that also were expressed after hCG stimulation. Cross-comparisons between the hCG and MEHP treatments revealed two genes, Anxa1 and AR1. We suggest that these genes may be involved in a new self-regulatory mechanism of steroidogenesis. The MEHP-induced decreases in hCG-stimulated steroid formation were paralleled by increases in reactive oxygen species generation, with the latter mediated by the Cyp1a1 gene and its network. A model for the mechanism of MEHP action on MA-10 Leydig cell steroidogenesis is proposed.

Citing Articles

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