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The Journal of Biochemistry
Year: 2009  |  Volume: 146  |  Issue: 1  |  Page No.: 113 - 122

Placenta Expressing the Greatest Quantity of Bisphenol A Receptor ERR{gamma} among the Human Reproductive Tissues: Predominant Expression of Type-1 ERR{gamma} Isoform

Y Takeda, X Liu, M Sumiyoshi, A Matsushima, M Shimohigashi and Y. Shimohigashi    

Abstract:

Estrogen-related receptor (ERR), one of the 48 human nuclear receptors, has a fully active conformation with no ligand. We recently demonstrated that ERR binds strongly bisphenol A (BPA), one of the nastiest endocrine disruptors, and thus retaining ERR's high basal constitutive activity. A report that BPA accumulates in the human maternal–fetal placental unit has led us to hypothesize that a large amount of ERR might exist in the human placenta. Here we report evidence that placenta indeed expresses ERR exceptionally strongly. We first ascertained the presence of nine different ERR mRNA variants and the resulting three ERR protein isoforms. By real-time PCR, we estimated the relative amount of ERR mRNA using total RNA extracts from human reproductive tissues. Placenta was found to express ERR extremely highly. Among the three ERR protein isoforms, placenta exclusively expresses the type-1 isoform, which possesses additional 23-mer amino-acid residues at the N-terminus of the ordinary ERR. This N-terminal elongation was found to elevate by approximately 50% the basal constitutive activity of ERR, as evidenced in the luciferase reporter gene assay. The present results suggest that BPA accumulates in the placenta by binding to ERR.

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