Effects of recombinant human FSH and hCG on the expression of interleukin-6 (IL-6) and vascular endothelial growth factor-A (VEGF-A) in human granulosa lutein cells and stimulation of VEGF-A expression by IL-6

Introduction: This study was performed to elucidate the effects of gonadotropins on the production of vascular endothelial growth factor-A (VEGF-A) and interleukin-6 (IL-6) and the effects of IL-6 on VEGF-A expression in human granulosa-lutein cells in vitro. Methods: Granulosa cells (GC) were isolated from follicular aspirates of patients undergoing ovarian stimulation for in vitro-fertilization (IVF). Cells were cultured with or without recombinant human follicle stimulating hormone (rhFSH) and human chorionic gonadotropin (hCG) at various concentrations and cellular expression of VEGF-A and IL-6 was analysed on the mRNA-level by Northern analysis. VEGF-A- and IL-6 protein in cell supernatants was measured by enzyme-linked immunosorbent assay (ELISA). Furthermore GC were stimulated with increasing doses of recombinant human IL-6 (rhIL-6) and VEGF-A production of GC was measured. Results: Stimulation of GC with either hCG or rhFSH led to a dose-dependent increase of VEGF-A- and IL-6 protein. Stimulation of GC with increasing doses of rhIL-6 led to a dose-dependent increase of VEGF-A protein. Conclusion: These findings suggest a gonadotropin dependent expression of VEGF and IL-6 in human GC. Furthermore IL-6 stimulates VEGF-A-production of GC. These interactions may be of pathophysiological significance for the development of OHSS.