Differential effects of natural and environmental estrogens on endothelin synthesis in bovine oviduct cells.
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 17beta-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 17beta-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 micromol/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 (alpha and beta), but the modulatory effects of estradiol, but not EEs, on ET-1 synthesis were blocked by ICI-182 780 (1 microM), 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.
Reinhart
Karin C
KC
Department of Obstetrics and Gynecology, Clinic for Endocrinology, University Hospital, 8091 Zurich, Switzerland.
Dubey
Raghvendra K
RK
Cometti
Barbara
B
Keller
Paul J
PJ
Rosselli
Marinella
M
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology*; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens; D028321:Plant Preparations / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism
D016232:Endothelins; D004785:Environmental Pollutants; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D011078:Polychlorinated Biphenyls