Effect of methoxychlor and estradiol on cytochrome P450 enzymes in the mouse ovarian surface epithelium

Daniel A. Symonds, Kimberly P. Miller, Dragana Tomic, Jodi A. Flaws

Research output: Contribution to journalArticlepeer-review

Abstract

Although the ovarian surface epithelium (OSE) is responsive to hormones and endocrine-disrupting chemicals, little information is available on the metabolizing capabilities of the OSE. Thus, we tested the hypothesis that the OSE is capable of expressing genes regulating phase I metabolism of estrogen and the estrogenic endocrine disruptor methoxychlor (MXC). To test this hypothesis, we isolated mouse OSE cells and cultured them with vehicle (dimethylsulfoxide; DMSO), 3 μM MXC, or 0.1 μM 17β-estradiol (E2) ± the anti-estrogen ICI 182,780 (1 μM) for 14 days. After culture, the cells were subjected to quantitative real-time polymerase chain reaction for cytochrome P450s (CYPs) 1A1, 1B1, 2C29, and 1A2, and estrogen receptor α (ERα). Our results indicate that E2 and MXC did not alter the expression of CYP1A1 or CYP1A2. In contrast, E2 significantly increased expression of CYP1B1 compared to controls (DMSO = 0.93 ± 0.1, E2 = 3.12 ± 0.64 genomic equivalents (GE), n= 4, p ≤ 0.01). The E2-induced increase in CYP1B1 was abolished by co-treatment with ICI 182,780 (0.41 ± 0.17 GE). MXC treatment did not affect CYP1B1 expression. Both MXC and E2 increased expression of CYP2C29 (DMSO = 0.02 ± 0.003; MXC = 0.04 ± 0.008; E2 = 0.46 ± 0.03 GE, n = 4, p ≤ 0.05). MXC- and E2-induced elevations in CYP2C29 were abolished by co-treatment with ICI 182,780 (0.02 ± 0.005; 0.02 ± 0.07 GE). In addition, E2 increased ERα expression 15-fold compared to controls (DMSO = 1.10 ± 0.09, E2 = 15.0 ± 3.60 GE, n = 3, p ≤ 0.05), and ICI 182,780 abolished the E2-induced increase in ERα expression (1.85 ± 1.09 GE). MXC treatment did not affect ERα expression. These data indicate that the OSE expresses enzymes known to metabolize native and xenoestrogens and that MXC and E2 modulate expression of some of them through ER-linked mechanisms.

Original languageEnglish (US)
Pages (from-to)510-514
Number of pages5
JournalToxicological Sciences
Volume89
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Keywords

  • Cytochrome P450
  • Estradiol
  • Estrogen receptor
  • Methoxychlor
  • Ovarian surface epithelium

ASJC Scopus subject areas

  • Toxicology

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