EXPRESSION OF THE GENES ENCODING THE INSULIN-LIKE GROWTH-FACTORS (IGF-I AND IGF-II), THE IGF AND INSULIN-RECEPTORS, AND IGF-BINDING PROTEINS-1-6 AND THE LOCALIZATION OF THEIR GENE-PRODUCTS IN NORMAL AND POLYCYSTIC-OVARY-SYNDROME OVARIES
EXPRESSION OF THE GENES ENCODING THE INSULIN-LIKE GROWTH-FACTORS (IGF-I AND IGF-II), THE IGF AND INSULIN-RECEPTORS, AND IGF-BINDING PROTEINS-1-6 AND THE LOCALIZATION OF THEIR GENE-PRODUCTS IN NORMAL AND POLYCYSTIC-OVARY-SYNDROME OVARIES
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DOI：
10.1210/jcem.78.6.7515389
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发表时间：
1994-06-01
影响因子：
5.8
通讯作者：
YEN, SSC
中科院分区：
文献类型：
--
作者：
ELROEIY, A;CHEN, XH;YEN, SSC
为了了解胰岛素样生长因子（IGFs）在多囊卵巢综合征（PCOS）中的潜在作用，我们检测了编码IGFs、IGFr、胰岛素受体（Ir）和IGFBPs-1-6的基因的表达，以及基因产物在正常和PCOS人卵巢特定细胞区室中的定位。信使核糖核酸（mRNA）的定位与特定的S-35标记的人反义RNA探针原位杂交，和蛋白质的免疫组化检测使用特定的抗血清。PCOS卵巢小窦卵泡（3-6 mm）的卵泡膜细胞（而非颗粒细胞（GC））同时表达IGF-I和IGF-II转录本。丰富的IGF-Ir mRNA仅在GC中发现，IGF-IIr mRNA在颗粒细胞和卵泡膜细胞中发现，Ir mRNA在所有细胞类型中检测到，包括颗粒细胞，卵泡膜细胞和基质细胞。基因产物的定位显示没有IGF-I免疫反应性，但是，其他基因产物的免疫染色与其相应的mRNA共定位。PCOS卵泡中mRNA和蛋白的细胞分布与正常卵巢小窦卵泡中观察到的无区别。然而，在优势卵泡中，IGF-I mRNA不再检测到，但丰富的IGF-II mRNA仅在GC中表达。在PCOS卵泡中，未检测到IGFBP-1 mRNA，IGFBP-2 mRNA在颗粒细胞和卵泡膜细胞中均有表达，IGFBP-3 mRNA仅在卵泡膜细胞中有表达，IGFBP-4和IGFBP-5 mRNA在所有细胞中均有表达，IGFBP-6 mRNA未检测到。通过免疫染色定位的基因产物显示，每个蛋白质与其相应的mRNA共定位。PCOS卵泡中IGFBP-1 mRNA和蛋白的细胞分布与正常卵巢小窦卵泡无明显区别，但优势卵泡中IGFBP-1 mRNA仅见于GC，IGFBP-2 mRNA见于卵泡膜细胞，IGFBP-3 mRNA见于颗粒细胞和卵泡膜细胞。IGFBP-4和IGFBP-5基因在所有类型的细胞中均有中度表达，包括基质细胞，但未检测到IGFBP-6 mRNA。同样，每个基因产物与其相应的mRNA共定位。1)虽然PCOS卵泡和优势卵泡之间存在显著差异，但编码IGFs、IGFrs、Ir和IGFBPs的mRNA的表达和蛋白质的定位与正常卵巢小窦卵泡中所见的相似，这表明在两种情况下卵泡成熟停滞可能涉及共同的机制。2)在PCOS卵泡和正常卵巢小窦卵泡GC中均未见IGFBP-1和IGFBP-3 mRNA表达，而IGFBP-2 mRNA表达丰富。因此，分泌的IGFBP-2可能在GC中起FSH作用的抑制剂的作用。3)在PCOS卵巢的所有细胞室中存在Ir mRNA和蛋白质，支持高胰岛素血症在PCOS卵巢高雄激素血症中的内分泌作用。
To discern the potential role of the insulin-like growth factors (IGFs) in polycystic ovary syndrome (PCOS), we examined the expression of the genes encoding the IGFs, IGF receptors (IGFr), insulin receptor (Ir), and IGF-binding proteins (IGFBPs-1-6) as well as the localization of the gene products in specific cellular compartments of normal and PCOS human ovaries. Messenger ribonucleic acid (mRNA) was localized by in situ hybridization with specific S-35-labeled human antisense RNA probes, and protein was detected by immunohistochemistry using specific antisera. Thecal cells, but not granulosa cells (GC), of small antral follicles (3-6 mm) from PCOS ovaries expressed both IGF-I and IGF-II transcripts. Abundant IGF-Ir mRNA was found only in GC, IGF-IIr mRNA was found in both granulosa and thecal cells, and Ir mRNA was detected in all cell types, including granulosa, thecal, and stromal cells. Localization of the gene products revealed no IGF-I immunoreactivity; however, immunostaining for each of the other gene products was colocalized with its corresponding mRNA. The cellular distribution of mRNA and protein in PCOS follicles was indistinguishable from that observed in small antral follicles from normal ovaries. In dominant follicles, however, IGF-I mRNA was no longer detectable, but abundant IGF-II mRNA was expressed exclusively in GC. Although IGF-Ir mRNA was expressed in CC, IGF-IIr mRNA was found in both granulosa and thecal cells.In follicles taken from PCOS ovaries, no IGFBP-1 mRNA was detected, IGFBP-2 mRNA was abundant in both granulosa and thecal cells, moderate IGFBP-3 mRNA was found only in thecal cells, IGFBP-4 and -5 mRNAs were present in all cellular compartments, and IGFBP-6 mRNA was not detected. Localization of the gene products by immunostaining revealed that each protein colocalized with its corresponding mRNA. The cellular distribution of IGFBP mRNA and protein in PCOS follicles was also indistinguishable from that in small antral follicles of normal ovaries, but remarkable differences were found in dominant follicles, where abundant IGFBP-1 mRNA was seen exclusively in GC, IGFBP-2 mRNA in thecal cells, and IGFBP-3 mRNA in both granulosa and thecal cells. Moderate expression of the IGFBP-4 and IGFBP-5 genes was seen in all cell types, including stromal cells, but no IGFBP-6 mRNA was detected. Again, each of the gene products colocalized with its corresponding mRNA.We conclude the following. 1) Although remarkable difference exist between PCOS follicles and dominant follicles, the expression of mRNAs encoding the IGFs, IGFrs, Ir, and IGFBPs and localization of the proteins are similar to those seen in small antral follicles of normal ovaries, suggesting that common mechanisms may be involved in follicular maturational arrest in both situations. 2) In GC of both PCOS follicles and small antral follicles of normal ovaries, no IGFBP-1 and IGFBP-3 mRNA were seen, whereas abundant IGFBP-2 mRNA was expressed. Thus, secreted IGFBP-2 may function as an inhibitor of FSH action in the GC. 3) The presence of Ir mRNA and protein in all cellular compartments of the PCOS ovary lends support to an endocrine role of hyperinsulinemia in ovarian hyperandrogenism in PCOS.