Progesterone induces the expression of vascular endothelial growth factor (VEGF) 120 and Flk-1, its receptor, in bovine granulosa cells

Vascular endothelial growth factor (VEGF) isoforms (VEGF 120 and VEGF 164) secreted by granulosa cells are involved in thecal angiogenesis during follicular development in the bovine ovary. The follicular fluid in the developing follicle includes a slight amount of the progesterone. However, the progesterone (P4) effects on VEGF120 and VEGF164 isoforms have not been well characterized in the bovine granulosa cells. We investigated the effects of progesterone on the gene expression of hypoxia-inducible factor 1α (HIF-1α, transcription factor), VEGF120, VEGF164 and Flk-1, its receptors, in cultured bovine granulosa cells. Messenger RNA expression for HIF-1α, VEGF120, VEGF164 and Flk-1 was quantified using real-time PCR methods. The levels of VEGF120, HIF-1α and Flk-1 mRNAs were increased significantly by P4 at a concentration of 10 ng/ml. In contrast, the expression of VEGF 164 gene is inhibited by P4. The level of VEGF120 and Flk-1 mRNAs in the granulosa cells treated with 10 ng/ml progesterone plus 1 ng/ml estradiol significantly decreased compared with progesterone alone. In contrast, the addition of 1 ng/ml estradiol to the culture medium increased the expression of VEGF164 gene. In conclusion, our data demonstrated that progesterone might stimulate the expression of the VEGF120 via HIF-1α, transcription factor, in bovine granulosa cells. These results suggest the hormone-dependent expression pattern of VEGF isoforms during follicular development. Thus, our study suggested the expression of VEGF isoforms in granulosa cells might be controlled by a different pathway during follicle development in cow.