Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 30, Issue 5, Pages 1233-1240Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2012.1122
Keywords
calbindin-D9k; bisphenol A; 4-tert-octylphenol; 4-nonylphenol; isobutylparaben; synergistic effects; GH3 cells
Categories
Funding
- Korea Food and Drug Administration [12182KFDA638]
- Vietnam National Foundation for Science and Technology Development (NAFOSTED) [106.06-2011.33]
- Food & Drug Administration (KFDA), Republic of Korea [17609-12182독평기638] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Various endocrine-disrupting chemicals (EDCs) such as bisphenol A (BPA), alkylphenols [4-nonylphenol (NP) and 4-tert octylphenol (OP)] and isobutylparaben (IBP) are a constant concern due to their widespread distribution. It has been reported that some combinations of hormone-disrupting chemicals are much more powerful than any of the chemicals alone. In this study, we measured the expression of an estrogenic biomarker gene, calbindin-D9k (CaBP-9k), and progesterone receptor (PR) to evaluate the individual or combined estrogenic activity of BPA, NP, OP and IBP in GH3 rat pituitary cells. Most doses of the individual compounds and all the doses of the combined chemicals significantly increased CaBP-9k and PR mRNA and protein expression compared to the vehicle (except for PR expression after treatment with OP and NP at 10(-7) M). Of note, high doses (10(-6) and 10(-5) M) of the EDC combinations increased the translational and transcriptional levels of CaBP-9k by 1.3- to 2.4-fold compared to each individual equivalent concentrations of EDCs. To determine whether the increased CaBP-9k gene expression was induced via intracellular estrogen receptor (ER), we blocked ER signaling using fulvestrant, an ER antagonist. The results showed that fulvestrant significantly reversed the CaBP-9k and PR upregulation following treatment with individual EDCs or their combinations. Taken together, we conclude that combinations of BPA, NP. OP and IBP in GH3 rat pituitary cells have synergistic estrogenic activities mediated by ER signaling. In addition, the expression of the CaBP-9k gene may be used as a biomarker to assess the synergistic effects of EDCs in vitro.
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