Effects of mifepristone on vascular endothelial growth factor and thrombospondin-1 mRNA in Ishikawa cells: implication for the endometrial effects of mifepristone

Mifepristone has been used for both medical termination of pregnancy and emergency contraception. Mifepristone may have both an antiovulatory activity and an antiproliferative effect on the endometrium. We have evaluated the effect of mifepristone on vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) using Ishikawa cells in vitro. Mifepristone, progesterone and 17beta-estradiol at concentrations of 1.0, 0.1 and 0.01 muM, were added to confluent cells and further cultured for additional 24 It. Total RNA was extracted from control and treated cells. After reverse transcription, VEGF, TSP-1 and beta-actin cDNAs were amplified with polymerase chain reaction spiked with 33p-dCTP. The relative abundance of VEGF 121 and 165 isoforms and TSP-1 mRNA were measured by scintillation spectroscopy. Mifepristone and progesterone did not stimulate VEGF mRNA 121 and 165 isoforms, while 17beta-estradiol increased both VEGF isoforms. Mifepristone did not stimulate TSP-1 mRNA at any concentration, but progesterone increased TSP-1 mRNA, and this effect was inhibited with mifepristone. 17beta-Estradiol did not increase TSP-1 expression. We hypothesized, based on these data, that the clinical finding of endometrial antiproliferative effect and low vaginal bleeding rate observed in women using mifepristone may be related to lack of stimulation of these angiogenic factors. (C) 2004 Elsevier Inc. All rights reserved.