Dong Mei, Huang Lili, Wang Wenjun, Du Miaomiao, He Zuanyu, Mo Yaqin, Yang Dongzi
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangdong, China.
Pharmazie. 2011 Jun;66(6):436-9.
With the progress of cancer treatment, fertility preservation has become an urgent requisition. Gonadotropin-releasing hormone agonist (GnRH-a) and antagonist (GnRH-ant) have been used to protect fertility for these patients. However, studies showed that although GnRH-a and GnRH-ant had a comparable down-regulating effect on the pituitary, GnRH-ant could not preserve ovarian function. Moreover, GnRH-ant alone could deplete primordial follicles. It might be speculated that an additional intraovarian system existed except the pituitary system. Anti-Müerian hormone (AMH) and Stem cell factor (SCF) proved to be the key factors in follicle recruitment and development. The balance between AMH and SCF was tightly related to ovarian reserve. To investigate the intraovarian effect of GnRH-a or GnRH-ant on ovarian reserve, we examined AMH and SCF expression in human granulosa cells (hGCs). GCs were isolated from follicular aspirates after oocyte removal from the patients undergoing assisted reproduction techniques. After pretreated with GnRH-a (triptorelin) or GnRH-ant (cetrorelix) for 48 h, mRNA and protein of AMH and SCF were analyzed by Real-time PCR and Immunoblot assay respectively. The results indicated that AMH mRNA and protein expressions were down-regulated in the GnRH-ant groups, SCF mRNA and protein expressions were up-regulated in the high-dose GnRH-ant group. There was no difference of AMH and SCF expression in the GnRH-a group or GnRH-a + GnRH-ant group compared with control. These results suggested the effects of GnRH-a and GnRH-ant on the regulation of AMH and SCF were different, which may provide insight into the mechanism of GnRH-a and GnRH-ant interventions on ovarian reserve.
随着癌症治疗的进展，生育力保存已成为一项紧迫的需求。促性腺激素释放激素激动剂（GnRH-a）和拮抗剂（GnRH-ant）已被用于保护这些患者的生育力。然而，研究表明，尽管GnRH-a和GnRH-ant对垂体具有相当的下调作用，但GnRH-ant无法维持卵巢功能。此外，单独使用GnRH-ant会消耗原始卵泡。推测可能除了垂体系统外还存在一个额外的卵巢内系统。抗苗勒管激素（AMH）和干细胞因子（SCF）被证明是卵泡募集和发育的关键因素。AMH和SCF之间的平衡与卵巢储备密切相关。为了研究GnRH-a或GnRH-ant对卵巢储备的卵巢内作用，我们检测了人颗粒细胞（hGCs）中AMH和SCF的表达。从接受辅助生殖技术的患者卵泡抽吸物中去除卵母细胞后分离出颗粒细胞。用GnRH-a（曲普瑞林）或GnRH-ant（西曲瑞克）预处理48小时后，分别通过实时PCR和免疫印迹分析检测AMH和SCF的mRNA和蛋白质。结果表明，GnRH-ant组中AMH的mRNA和蛋白质表达下调，高剂量GnRH-ant组中SCF的mRNA和蛋白质表达上调。与对照组相比，GnRH-a组或GnRH-a + GnRH-ant组中AMH和SCF的表达没有差异。这些结果表明GnRH-a和GnRH-ant对AMH和SCF的调节作用不同，这可能为GnRH-a和GnRH-ant干预卵巢储备的机制提供见解。
