San Roman G A, Magoffin D A
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center/University of California School of Medicine, Los Angeles 90048.
J Clin Endocrinol Metab. 1993 Mar;76(3):625-32. doi: 10.1210/jcem.76.3.7680354.
An increasing body of evidence suggests a regulatory role for insulin-like growth factor-binding proteins (IGFBPs) in ovarian folliculogenesis. Although IGFBPs have been identified in the follicular fluid (FF) from women undergoing hyperstimulation for in vitro fertilization, little is known about the pattern of IGFBP expression during follicle development in natural menstrual cycles. The purpose of the present study was to determine the pattern of IGFBPs in the FF of healthy and atretic follicles during the follicular phase of natural menstrual cycles. FF was aspirated from follicles in normal ovaries of regularly cycling women. Dominant follicles were identified as the largest follicle in either ovary with an androstenedione to estradiol ratio in the FF of 4 or less. The androstenedione/estradiol ratio in atretic follicles was greater than 4. IGFBPs in the FF samples were analyzed by ligand blotting with [125I]IGF-II. The identities of the BPs measured by ligand blotting were confirmed by immunoblot and RIA analysis. IGFBP-3 concentrations decreased in healthy follicles as the follicular phase progressed. IGFBP-3 levels were significantly lower in dominant than healthy cohort follicles. IGFBP-2 was elevated in atretic follicles relative to that in healthy follicles. The levels of a 29-kilodalton BP comigrating with IGFBP-1 did not change significantly. IGFBP-4 was detected in only some of the atretic follicles. These experiments demonstrate that 1) at least four distinct IGFBPs are present in FF of women with natural unstimulated menstrual cycles; 2) IGFBP-3 in FF decreases during folliculogenesis, and 3) IGFBP-2 levels are elevated in atretic follicles. These data support the concept that IGFBPs may play important roles in regulating follicle selection and atresia.
越来越多的证据表明胰岛素样生长因子结合蛋白（IGFBPs）在卵巢卵泡发生过程中具有调节作用。尽管在接受体外受精超刺激的女性卵泡液（FF）中已鉴定出IGFBPs，但对于自然月经周期中卵泡发育过程中IGFBP表达模式却知之甚少。本研究的目的是确定自然月经周期卵泡期健康卵泡和闭锁卵泡的FF中IGFBPs的模式。从规律月经周期女性的正常卵巢卵泡中抽吸FF。优势卵泡被确定为两侧卵巢中最大的卵泡，其FF中雄烯二酮与雌二醇的比值为4或更低。闭锁卵泡中雄烯二酮/雌二醇的比值大于4。通过用[125I]IGF-II进行配体印迹分析FF样本中的IGFBPs。通过免疫印迹和放射免疫分析确认配体印迹法测定的结合蛋白的身份。随着卵泡期的进展健康卵泡中IGFBP-3浓度降低。优势卵泡中的IGFBP-3水平明显低于健康队列卵泡。相对于健康卵泡，闭锁卵泡中IGFBP-2升高。与IGFBP-1共迁移的29千道尔顿结合蛋白的水平没有显著变化。仅在一些闭锁卵泡中检测到IGFBP-4。这些实验表明：1）在自然未受刺激月经周期的女性FF中至少存在四种不同的IGFBPs；2）FF中的IGFBP-3在卵泡发生过程中降低，以及3）闭锁卵泡中IGFBP-2水平升高。这些数据支持IGFBPs可能在调节卵泡选择和闭锁中起重要作用的概念。
