Synergistic effects of growth hormone and insulin-like growth factor-I on differentiation and replication of cultured human luteinized granulosa cells

Background. The present study was designed to assess the effects of insulin-like growth factor-I (IGF-I) alone and in combination with growth hormone (GH) on differentiation and replication in cultured human granulosa cells. Methods. Granulosa cells from patients undergoing in vitro fertilization were isolated and cultured for 2 days in culture medium with 10% serum, the medium was removed and the cells were incubated with IGF-I (1, 10 and 100 ng/ml) with or without GH (10 ng/ml) in serum-free medium and in the presence of H-3-methylthymidine (2 mu Ci/ml). Results. IGF-I alone resulted in a significant dose-dependent increase in medium estradiol (E-2) (p<0.05) and progesterone (P) (p<0.001) and suppression of IGF-binding protein-1 (IGFBP-1) (p<0.001), without any increase in [H-3]-thymidine incorporation (P=0.10). The combination of IGF-I and GH further increased the release of E-2 (p<0.001), and the amount of [H-3]-thymidine incorporation (p<0.001). Conclusion. These results indicate a synergistic effect of IGF-I and GH on differentiation and replication of human granulosa cells, and thus support a role of both GH and IGF-I in regulation of ovarian function.