ABSTRACT
We previously isolated a bisphenol A (BPA)-binding protein from rat brain and showed that it was identical to the protein disulfide isomerase (PDI), which also serves as a 3,3',5-triiodo-l-thyronine (T3)-binding protein. In this study, we investigated the effects of BPA on the production of growth hormone (GH) in GH3 cells and examined the possible involvement of PDI in this process. When administered singly, BPA and T3 each induced GH release in GH3 cells. When cells were treated with the combination of BPA and T3, the release of GH was much greater than that by T3 alone, but GH mRNA and promoter activity were not increased. These results suggested that the synergistic effect of T3 plus BPA on GH release was due to posttranslational regulation. Over-expression of PDI suppressed GH mRNA expression and GH release, suggesting that PDI modulates the T3-induced gene expression. We conclude that BPA can disrupt the thyroid hormone function in GH3 cells, and GH release induced by T3 is influenced by expression of PDI.
Subject(s)
Air Pollutants, Occupational/antagonists & inhibitors , Growth Hormone/metabolism , Phenols/antagonists & inhibitors , Pituitary Gland/enzymology , Protein Disulfide-Isomerases/metabolism , Triiodothyronine/antagonists & inhibitors , Air Pollutants, Occupational/pharmacology , Animals , Benzhydryl Compounds , Cell Line, Tumor , Gene Expression , Growth Hormone/genetics , Phenols/pharmacology , Pituitary Gland/drug effects , Protein Disulfide-Isomerases/genetics , RNA, Messenger/analysis , RNA, Messenger/metabolism , Rats , Triiodothyronine/metabolism , Triiodothyronine/pharmacologyABSTRACT
AIM: To study the effect of bisphenol A on the epididymis and epididymal sperm of rats and the possible amelioration action of co-administration with vitamin C. METHODS: Male Wistar rats were orally administered bisphenol A (0.2 microg x kg (-1) x day(-1), 2 microg x kg(-1) x day(-1) and 20 microg x kg(-1) x day(-1)) and 0.2 microg, 2 microg and 20 microg bisphenol A + 40 mg vitamin C x kg(-1) x day(-1) for 60 days. On day 61, rats were killed with anesthetic ether and sperm collected from epididymis were used or assessment of sperm count, motility and viability and biochemical studies. A 1 % homogenate of epididymis was prepared and used for biochemical estimations. Caput, corpus and cauda epididymis were fixed in Bouin's fixative for histological studies. RESULTS: Administration of bisphenol A caused a reduction in the epididymal sperm motility and count and the sperm viability remained unchanged. The activities of superoxide dismutase and glutathione peroxidase decreased, while the levels of lipid peroxidation increased in epididymal sperm and epididymis at all doses. Co-administration with vitamin C reversed the effect of bisphenol A-induced oxidative stress in epididymal sperm and epididymis. A complete degeneration of epididymal epithelium in caput, corpus and cauda regions with reduction in the number of sperms were observed at all doses of bisphenol A-treated rats. CONCLUSION: Bisphenol A induced oxidative stress in epididymis and caused degeneration of the epididymal epithelium of rats. Co-administration with vitamin C had a protective effect against the bisphenol A-induced toxicity in epididymal sperm and epididymis.
