There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.

译文

:现在有大量证据表明胰岛素样生长因子(IGF)在人卵巢中起重要作用。最近也已经很明显,IGF的生理活性受到许多特异性结合蛋白(IGFBP)的调节。为了理解IGF在卵巢生理中的作用,将需要表征这些IGFBP的存在和功能。作为对此的第一步,我们通过Western配体印迹研究了各种结合蛋白的存在,并测量了19种正常人从未刺激的优势和同类卵泡中获得的卵泡液(FF)中其中一种IGFBP-1的水平。女性和8例多囊性卵巢癌患者和1例多囊性卵巢癌患者。在正常女性中,优势卵泡中的IGFBP-1水平与匹配的血清水平相似,但在同龄卵泡中则显着降低。 IGFBP-1水平与FF量(r = 0.58,P小于0.001)和成对的血清水平(r = 0.63,P小于0.001)相关。在LH激增后的主要卵泡中,这种与血清水平的关系不再成立,在9名受试者中,有3名的FF水平高于血清。因此,正常人FF中的IGFBP-1似乎部分来自循环,但在较大的发育中的优势卵泡中有额外的局部产生。 Western配体印迹显示FF中有5种IGF结合蛋白与血清中鉴定的蛋白平行运行,这表明先前在血清中鉴定出的IGFBP种类也可能存在于FF中。如在血清中,对应于大(150kDa)结合复合物组分的位置上的两个条带是主要形式,在大多数FF样品中,它们甚至比随附的血清样品中更为突出。这与先前的淋巴研究相反,后者表明150kDa的复合物主要保留在循环系统中。 FF样本之间的所有三个小型IGFBP甚至在一个个体中都存在很大差异。每个IGFBP均独立于其他IGFBP而变化。我们的结果表明,FF中至少存在4个离散的IGFBP,提示每个子可能在卵巢内独立产生。

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