Yoshimura Y, Nagamatsu S, Ando M, Iwashita M, Oda T, Katsumata Y, Shiokawa S, Nakamura Y
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan.
Endocrinology. 1996 Feb;137(2):438-46. doi: 10.1210/endo.137.2.8593787.
The effects of insulin-like growth factor binding proteins (IGFBPs) on human CG (hCG)-induced oocyte maturation, ovulation, steroidogenesis, and intrafollicular plasminogen activator (PA) activity were investigated in rabbit ovaries perfused in vitro. The addition of IGFBP-3, but not IGFBP-1, to the perfusate dose dependently inhibited hCG-induced ovulation, whereas ovulation failed to occur in any ovaries perfused with medium or IGFBP-3 alone. IGFBP-3 (100 ng/ml) significantly inhibited the resumption of meiosis in ovulated ova and follicular oocytes in hCG-treated ovaries, as well as the hCG-stimulated production of estradiol (E2), but not progesterone, by the perfused ovaries. Intrafollicular PA activity increased significantly within 1 h after exposure to hCG, reaching a maximum at 4 h; IGFBP-3 significantly inhibited hCG-stimulated intrafollicular PA activity. The blockade of hCG-induced ovulation by IGFBP-3 correlated with the reduction in intrafollicular PA activity. Treatment with hCG induced a 2.5-fold increase in intrafollicular IGF-I messenger RNA levels at 4 h. Although ovulation failed to occur in ovaries treated with IGF-I (100 ng/ml) in the absence of gonadotropin, IGF-I significantly increased the mean diameter of preovulatory follicles and stimulated the resumption of meiosis in follicular oocytes. These effects of IGF-I on follicular growth and oocyte maturation were significantly inhibited by IGFBP-3 (100 ng/ml). Furthermore, IGFBP-3 significantly inhibited the IGF-I-stimulated production of E2. In conclusion, IGFBP-3, but not IGFBP-1, blocked the stimulatory effects of hCG in the ovulatory process. These findings suggest that IGFBP-3 may contribute to the regulation of intrafollicular PA activity during follicular development and ovulation evoked by gonadotropin exposure, at least in part, via neutralizing endogenously produced IGF-I.
在体外灌注的兔卵巢中，研究了胰岛素样生长因子结合蛋白（IGFBPs）对人绒毛膜促性腺激素（hCG）诱导的卵母细胞成熟、排卵、类固醇生成及卵泡内纤溶酶原激活物（PA）活性的影响。向灌注液中添加IGFBP-3而非IGFBP-1，可剂量依赖性地抑制hCG诱导的排卵，而单独用培养基或IGFBP-3灌注的任何卵巢均未发生排卵。IGFBP-3（100 ng/ml）显著抑制hCG处理的卵巢中排卵卵母细胞和卵泡卵母细胞减数分裂的恢复，以及灌注卵巢中hCG刺激的雌二醇（E2）而非孕酮的产生。暴露于hCG后1小时内，卵泡内PA活性显著增加，4小时达到最大值；IGFBP-3显著抑制hCG刺激的卵泡内PA活性。IGFBP-3对hCG诱导排卵的阻断与卵泡内PA活性的降低相关。hCG处理4小时后，卵泡内IGF-I信使核糖核酸水平增加2.5倍。尽管在无促性腺激素的情况下，用IGF-I（100 ng/ml）处理的卵巢未发生排卵，但IGF-I显著增加了排卵前卵泡的平均直径，并刺激卵泡卵母细胞减数分裂的恢复。IGFBP-3（100 ng/ml）显著抑制了IGF-I对卵泡生长和卵母细胞成熟的这些作用。此外，IGFBP-3显著抑制IGF-I刺激的E2产生。总之，IGFBP-3而非IGFBP-1阻断了hCG在排卵过程中的刺激作用。这些发现表明，IGFBP-3可能至少部分通过中和内源性产生的IGF-I，在促性腺激素暴露诱发的卵泡发育和排卵过程中，对卵泡内PA活性的调节起作用。
