Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells

Toxicology and Applied Pharmacology
T N Lovekamp, B J Davis

Abstract

The female reproductive toxicity of di-(2-ethylhexyl) phthalate and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) is attributed to suppression of ovarian granulosa cell estradiol production. In these studies, several structurally related phthalates (0-200 microM) and Wy-14,643 (0-100 microM) were compared to MEHP for their effects on granulosa cell estradiol production and transcript levels of cytochrome P450 enzyme CYP 19, also known as aromatase (P450arom), the rate-limiting enzyme in the conversion of androgens to estrogens. Granulosa cells were obtained from 28-day-old Fisher 344 rats and were cultured for 48 h. Test chemical or DMSO was added at the time of culture, along with testosterone as a substrate for aromatase. 17beta-Estradiol production was measured by standard radioimmunoassay, mRNA was measured by fluorescent RT-PCR, and protein was measured by Western blot analysis. MEHP was unique among the phthalates in its ability to decrease estradiol production, while Wy-14,643 had effects similar to MEHP at 100 microM. MEHP and Wy-14,643 also significantly decreased aromatase mRNA levels. The decrease in mRNA was concentration dependent and was paralleled by a decrease in aromatase protein. MEHP did not alte...Continue Reading

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Citations

Jun 8, 2006·Journal of Assisted Reproduction and Genetics·Takehiro SerikawaKenichi Tanaka
Apr 28, 2012·Journal of Assisted Reproduction and Genetics·Stephan P KrotzJohn E Buster
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Feb 27, 2010·Environmental Health Perspectives·Jennifer WeuveLauren A Wise
Feb 8, 2003·Environmental Health Perspectives·Tara Lovekamp-Swan, Barbara J Davis
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Sep 24, 2014·Biochemical and Biophysical Research Communications·Qian GaoWen-Jie Li
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Jun 1, 2014·Environment International·Marijke de Cock, Margot van de Bor
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