Iwashita M, Kudo Y, Yoshimura Y, Adachi T, Katayama E, Takeda Y
Maternal and Perinatal Center, Tokyo Women's Medical College, Japan.
Horm Res. 1996;46 Suppl 1:31-6. doi: 10.1159/000185179.
Insulin-like growth factor (IGF)-I and IGF-II, and their binding proteins (IGFBPs) have been demonstrated to play important roles in follicular development as intraovarian regulators. Previous studies have demonstrated that the follicular fluid of atretic follicles contains high levels of IGFBP-2 and IGFBP-4, which are known to inhibit the action of IGFs. In this study, we identified IGFBP-4 protease activity in the follicular fluid of developing but not atretic follicles. To elucidate the regulation mechanism of IGFBP-4 proteolytic activity in the ovary, cultured luteinized granulosa cells (GCs) were incubated with various hormones, and proteolyzed IGFBP-4 in the medium was analyzed. IGFBP-4 proteolytic activity was increased when GCs were incubated with IGFs, estradiol or follicle-stimulating hormone (FSH) but not with testosterone. We also showed that IGFBP-4 inhibited IGF-1-induced estradiol release by GCs while proteolyzed IGFBP-4 did not. These results suggest that human luteinized GCs produce IGFBP-4 protease, and that FSH and IGFs may stimulate folliculogenesis by modulating IGFBP-4 degradation in the ovary.
胰岛素样生长因子（IGF）-I和IGF-II及其结合蛋白（IGFBPs）已被证明作为卵巢内调节因子在卵泡发育中发挥重要作用。先前的研究表明，闭锁卵泡的卵泡液中含有高水平的IGFBP-2和IGFBP-4，已知它们会抑制IGFs的作用。在本研究中，我们在发育中的而非闭锁卵泡的卵泡液中鉴定出了IGFBP-4蛋白酶活性。为了阐明卵巢中IGFBP-4蛋白水解活性的调节机制，将培养的黄素化颗粒细胞（GCs）与各种激素一起孵育，并分析培养基中被蛋白水解的IGFBP-4。当GCs与IGFs、雌二醇或促卵泡激素（FSH）孵育时，IGFBP-4蛋白水解活性增加，而与睾酮孵育时则没有增加。我们还表明，IGFBP-4抑制IGF-1诱导的GCs释放雌二醇，而被蛋白水解的IGFBP-4则不会。这些结果表明，人黄素化GCs产生IGFBP-4蛋白酶，并且FSH和IGFs可能通过调节卵巢中IGFBP-4的降解来刺激卵泡发生。
