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1 April 2003 Differential Effects of Natural and Environmental Estrogens on Endothelin Synthesis in Bovine Oviduct Cells
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Endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide that plays an important role within the endocrine/reproductive system, is synthesized by oviduct cells and regulates tubal contractility. Because 17β-estradiol (estradiol) regulates oviduct function by influencing the synthesis of autocrine/paracrine factors, estradiol may also regulate ET-1 synthesis. Furthermore, environmental estrogens (EEs; phytoestrogens and xenoestrogens), which structurally resemble estradiol and possess estrogenic activity, may mimic the effects of estradiol on ET-1 synthesis and may influence the reproductive system. Using cultures of bovine oviduct cells (epithelial cells:fibroblasts, 1:1), we investigated and compared the modulatory effects of estradiol, phytoestrogens, and xenoestrogens on ET-1 synthesis and determined whether these effects were estrogen receptor (ER) mediated. A quantitative ELISA for ET-1 in the culture medium revealed that 17β-estradiol inhibits ET-1 synthesis in a concentration-dependent manner (4–400 nmol/L). In contrast to estradiol, ET-1 synthesis was induced in cell cultures treated with xenoestrogens in the following order of potency (0.1 μmol/L): 4-hydroxy-trichlorobiphenyl > 4-hydroxy-dichlorobiphenyl > trichlorobiphenyl. The stimulatory effects of xenoestrogens on ET-1 production were mimicked by the phytoestrogens biochanin-A and genistein but not by formononetin, equol, and daidzein. The oviduct cells expressed both ERs (α and β), but the modulatory effects of estradiol, but not EEs, on ET-1 synthesis were blocked by ICI-182 780 (1 μM), a pure ER antagonist. Our results provide evidence that estradiol inhibits ET-1 synthesis in oviduct cells via an ER-dependent mechanism, whereas, EEs induce ET-1 synthesis via an ER-independent mechanism. The contrasting effects of EEs on ET-1 synthesis suggests that EEs may act as endocrine modulators/disruptors and may have deleterious effects on the reproductive system by adversely influencing the biology and physiology of the oviduct.

Karin C. Reinhart, Raghvendra K. Dubey, Barbara Cometti, Paul J. Keller, and Marinella Rosselli "Differential Effects of Natural and Environmental Estrogens on Endothelin Synthesis in Bovine Oviduct Cells," Biology of Reproduction 68(4), 1430-1436, (1 April 2003).
Received: 17 April 2002; Accepted: 1 November 2002; Published: 1 April 2003

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