LH/HCG stimulation of VEGF and adrenomedullin production by follicular fluid macrophages and luteinized granulosa cells

Luteinized granulosa cells and macrophages actively secrete vascular endothelial growth factor (VEGF) and adrenomedullin in the human ovulatory follicle. LH/human chorionic gonadotrophin (HCG) directly stimulates VEGF synthesis by granulosa cells while adrenomedullin may play a role in the process of luteinization. The current study examines whether pure human LH and HCG directly stimulate VEGF and adrenomedullin production by follicular fluid macrophages and granulosa cells. Macrophages and granulosa cells were obtained from pooled follicular aspirates of five individual patients during oocyte retrieval for IVF treatment. The cells were cultured in medium alone (control) or in medium supplemented with 1 IU/ml recombinant HCG (rHCG) or 6 IU/ml recombinant LH (rLH) for up to 7 days. VEGF production by macrophages was about five- or six-fold enhanced after 5 and 7 days by culture in the presence of rHCG or rLH when compared with control cultures. This effect was less pronounced on granulosa cells. Conversely, treatment with rHCG or rLH had no effect on the production rate of adrenomedullin neither in macrophages nor in granulosa cells. The effects of rHCG and rLH on VEGF production by granulosa cells or macrophages in culture were similar. This study suggests for the first time that LH-like gonadotrophins may directly stimulate VEGF but not adrenomedullin synthesis by follicular fluid macrophages.