Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17β-estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa cells

Objective: To determine the effect of 17beta-E-2, levonorgestrel, medroxyprogesterone acetate, and norethindrone on the expression of vascular endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro. Design: Prospective basic research study. Setting: Basic research laboratory. Patient(s): None. Intervention(s): Ishikawa cells were cultured in vitro. After 24 hours' incubation in serum-free media, 1.0, 0.1, and 0.01 muM concentrations of E-2, levonorgestrel, medroxyprogesterone acetate, and norethindrone were added for a further 24 hours of incubation. Main Outcome Measure(s): Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with P-actin as an internal control. Result(s): Estradiol stimulated VEGF isoforms 121 and 165. The progestins studied increased mRNA for VEGF isoforms 121 and 165 at all doses. Medroxyprogesterone acetate resulted in the greatest increase in both VEGF 121 and 165 compared with norethindrone and levonorgestrel. Conclusion(s): Estradiol and progestins increased VEGF 121 and 165 isoform mRNA in Ishikawa cells in vitro. We hypothesize that differences in VEGF expression may be associated with the irregular bleeding during progestin use in clinical situations. (C) 2004 by American Society for Reproductive Medicine.)