Yoshimura Y, Aoki N, Sueoka K, Miyazaki T, Kuji N, Tanaka M, Kobayashi T
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
J Clin Invest. 1996 Jul 15;98(2):308-16. doi: 10.1172/JCI118794.
The interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system (RAS) in follicular growth and ovulation were studied with the use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur in either control ovaries or the experimental ovaries perfused with IGF-I in a concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries perfused with IGF-I for 12 h was significantly correlated with the secretion rate of Ang II-IR at 12 h after exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG-induced ovulation in a dose-dependent manner. In addition, IGFBP-3 significantly reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by hCG administration. Intrafollicular plasminogen activator (PA) activity significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared with that in control ovaries perfused with medium alone. The concomitant addition of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I. However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in vitro stimulated both follicular growth and the intrafollicular Ang II-IR content. In conclusion, IGF-I enhances both ovarian Ang II production and follicular development by stimulating intrafollicular PA activity.
利用离体灌注兔卵巢制备物，研究了胰岛素样生长因子-I（IGF-I）与肾素-血管紧张素系统（RAS）在卵泡生长和排卵中的相互作用。在无促性腺激素的情况下，对照组卵巢或灌注浓度为1、10或100 ng/ml IGF-I的实验性卵巢均未发生排卵。暴露于IGF-I以剂量依赖方式刺激灌注兔卵巢中血管紧张素II样免疫反应性（Ang II-IR）的分泌率。灌注IGF-I 12小时的卵巢中卵泡直径增加百分比与暴露于IGF-I 12小时后Ang II-IR的分泌率显著相关。在无促性腺激素的情况下，向灌注液中添加IGFBP-3不会诱导排卵，但暴露于IGFBP-3会以剂量依赖方式抑制hCG诱导的排卵。此外，IGFBP-3显著降低了hCG给药刺激的卵巢Ang II-IR和前列腺素的分泌率。与仅用培养基灌注的对照卵巢相比，暴露于100 ng/ml IGF-I后4小时内，卵泡内纤溶酶原激活物（PA）活性显著增加。在暴露于IGF-I后4、6和8小时，向灌注液中同时添加IGFBP-3可显著降低IGF-I刺激的排卵前卵泡中的PA活性。然而，单独的IGFBP-3既不影响卵巢Ang II-IR的分泌率，也不影响卵泡内PA活性。体外暴露于外源性PA链激酶可刺激卵泡生长和卵泡内Ang II-IR含量。总之，IGF-I通过刺激卵泡内PA活性增强卵巢Ang II产生和卵泡发育。
