Vascular endothelial growth factor (VEGF) and angiopoietin regulation by gonadotrophin and steroids in macaque granulosa cells during the peri-ovulatory interval

The role of endothelial cell-specific growth factors in the vascularization of the primate peri-ovulatory follicle was examined, Experiments were desi gned firstly to detect expression of vascular endothelial growth factor (VE GF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in granulosa cells a nd secondly, to determine whether gonadotrophins and/or steroids regulate t heir expression during the peri-ovulatory interval. Granulosa cells and fol licular fluid were collected from rhesus macaques undergoing ovarian stimul ation before (0 h), 12, or 36 h after a bolus of ovulatory human chorionic gonadotrophin (HCG), with or without steroid ablation and progestin replace ment. VEGF; Ang-1 and Ang-2 mRNA were all detected prior to the ovulatory s timulus. Whereas follicular fluid VEGF concentrations increased 6-fold (P < 0.05) between 0 and 12 h, VEGF mRNA values were unchanged and were unaffec ted by steroid ablation. Ang-l mRNA decreased from 0 to 12 h (P < 0.05), fo llowed by a 30-fold increase (P < 0.05) at 36 h, while Ang-2 mRNA values we re unchanged between 0, 12 and 36 h. Steroid ablation decreased (P < 0.05) Ang-1 mRNA at 36 h, and Ang-2 mRNA at 12 h, while only Ang-1 was restored b y progestin replacement. These data suggest a dynamic expression of vascula r-specific growth factors in a gonadotrophin-dependent, steroid-independent (VEGF) or steroid-dependent (Ang-1) manner in granulosa cells of peri-ovul atory follicles of primates.