Holly J M, Eden J A, Alaghband-Zadeh J, Carter G D, Jemmott R C, Cianfarani S, Chard T, Wass J A
Department of Chemical Endocrinology, St Bartholomew's Hospital, London, UK.
Clin Endocrinol (Oxf). 1990 Jul;33(1):53-64. doi: 10.1111/j.1365-2265.1990.tb00465.x.
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.
现在有大量证据表明，胰岛素样生长因子（IGFs）在人类卵巢中发挥着重要作用。最近还发现，IGFs的生理活性受到多种特异性结合蛋白（IGFBPs）的调节。为了了解IGFs在卵巢生理学中的作用，需要对这些IGFBPs的存在和功能进行表征。作为迈向这一目标的第一步，我们通过Western配体印迹法研究了各种结合蛋白的存在情况，并测量了19名正常女性以及8名多囊卵巢患者和1名多房性卵巢患者未受刺激的优势卵泡和同期卵泡的卵泡液（FF）中其中一种结合蛋白IGFBP-1的水平。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，但同期卵泡中的水平显著较低。IGFBP-1水平与FF体积相关（r = 0.58，P < 0.001），与配对血清水平相关（r = 0.63，P < 0.001）。在促黄体生成素峰后的优势卵泡中，这种与血清水平的关系不再成立，9名受试者中有3名的FF水平高于血清水平。因此，正常人类FF中的IGFBP-1似乎部分来源于循环，但在较大的发育中的优势卵泡中还有额外的局部产生。Western配体印迹法显示，FF中有5种IGF结合蛋白与血清中鉴定出的蛋白平行，这表明先前在血清中鉴定出的IGFBP种类也可能存在于FF中。与血清中一样，对应于大（分子量150kDa）结合复合物成分位置的两条带是主要形式，在大多数FF样本中，这些带甚至比伴随的血清样本中更明显。这与先前在淋巴中的研究形成对比，先前的研究表明150kDa复合物大部分保留在循环中。即使在个体内部，所有三种小的IGFBPs在FF样本之间也有很大差异；每种IGFBP的变化独立于其他IGFBPs。我们的结果表明，FF中至少存在四种不同的IGFBPs，并表明每种可能在卵巢内独立产生。
