Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary
Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary
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DOI：
10.1095/biolreprod.104.034454
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发表时间：
2005-03-01
影响因子：
3.6
通讯作者：
Tesone, M
中科院分区：
文献类型：
--
作者：
Parborell, F;Irusta, G;Tesone, M
GnRH类似物，包括激动剂（GnRH-a）和拮抗剂（GnRH-ant），已被广泛用于抑制促性腺激素垂体释放。除了GnRH类似物对垂体-性腺轴的作用外，研究表明GnRH具有垂体外作用，特别是对大鼠和人类卵巢。在本研究中，我们评价了GnRH-a、醋酸亮丙瑞林（LA）或GnRH-ant、Antide（Ant）单独或共同对青春期前hCG治疗大鼠卵巢卵泡发育的直接体内作用。LA显着降低卵巢重量，而蚂蚁增加卵巢重量与对照组相比，然而，共注射两种化合物没有影响。此外，LA可增加窦前卵泡（PF）和闭锁卵泡的数量，减少早期窦卵泡（EAFs）和排卵前卵泡（POFs）的数量。Ant的共注射干扰了这种LA效应。与对照组相比，单独的Ant增加了POF的数量。细胞凋亡的分析表明，LA增加PF、EAF和POF中凋亡细胞的百分比;然而，Ant阻止了这种作用。此外，Ant单独降低EAF和POF中凋亡细胞的百分比。数据显示，Ant本身抑制BAX从细胞质到线粒体的易位，并将细胞色素C保留在线粒体中，而LA诱导细胞色素C释放。我们的结论是，蚂蚁通过减少BAX易位到线粒体抑制排卵前卵泡的细胞凋亡，这表明GnRH可能作为一种生理性卵巢内调节因子，能够通过增加BCL-2家族成员之间的不平衡介导的凋亡事件来干扰卵泡发育。
Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extra-pituitary effects, particularly on rat and human ovaries. In the present study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian follicular development in prepubertal eCG-treated rats. LA significantly decreased ovarian weight, whereas Ant increased ovarian weight compared with controls; however, coinjection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased the number of POFs compared with that of controls. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release. We conclude that Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX translocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor that is able to interfere with follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members.