Modulation of the intracellular calcium level in mammalian cells caused by 17β-estradiol, different phytoestrogens and the anti-estrogen ICI 182780

Abstract

In previous investigations it was shown that the synthetic estrogen diethylstilbestrol (DES) induces a rise of the intracellular calcium level ([Ca 2+] i) in C6 rat glioma cells [P. Tas, H. Stopper, K. Koschel, D. Schiffmann, Influence of the carcinogenic oestrogen diethylstilboestrol on the intracellular calcium level in C6 rat glioma cells. Toxic. In vitro 5 (1991) 463–465] which is accompanied by changes of the arrangement of the cytoskeleton. In the present study, we compared the induction of these effects in COS (monkey kidney cells) lacking estrogen receptors (ER) with those in RUCA-I (rat endometrial carcinoma) cells containing ER. The [Ca 2+] i in RUCA-I and COS cells following 17β-estradiol (ES), genistein (GEN), daidzein (DZ) and coumestrol (CES) treatment was analyzed. A significant increase of [Ca 2+] i induced by all compounds was observed in RUCA-I cells. No effects were detected in COS cells after ES and GEN treatment. The anti-estrogen ICI 182780 completely blocked the ES-and GEN-induced rise of [Ca 2+] i. Dose and time dependencies of changes of calcium levels were analyzed and a biphasic response could be observed. The actin staining showed disintegrated stress fibers in RUCA-I cells. The degree of the observed effects correlates with the known estrogenicity of the applied compounds (DES>ES>GEN). It remains to be elucidated whether or not the effects observed are mediated by the “classic” genomic estrogen receptor pathway or by alternate nongenomic or receptor-independent pathways.