Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary

Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary
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DOI:
10.1210/en.2005-0386
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发表时间:
2006-01-01
期刊:
影响因子:
4.8
通讯作者:
Ojeda, SR
Ojeda, SR
中科院分区:
医学2区
文献类型:
--
作者:
Dissen, GA;Garcia-Rudaz, C;Ojeda, SR

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胰岛素受体相关受体(IRR)是胰岛素受体家族的一员,它本身既不识别胰岛素,也不识别任何已识别的胰岛素相关肽。在神经系统和外周组织中,在也表达trkA(神经生长因子酪氨酸激酶受体)的细胞中检测到IRR mRNA。在卵巢中,当促性腺激素在排卵前激增时,trkA基因在大窦卵泡的鞘间质细胞中短暂激活。目前的研究表明,IRR基因在同一个卵巢腔室中表达,IRR mRNA含量在第一次发情的下午在这些细胞中显著增加,并且-与trkA mRNA的情况一样-增加是由促性腺激素引起的。受影响的主要是编码全长受体的IRR mRNA种类;其丰度的增加伴随着IRR蛋白含量的相应变化。使用多种方法进行广泛的分子搜索,包括筛选cDNA文库和用退化引物进行PCR扩增,均未发现IRR配体。对来自脊椎动物的20个胰岛素相关序列和15个松弛素家族肽的系统发育分析表明,哺乳动物基因组不太可能含有与胰岛素家族密切相关的独特基因表达的额外配体。尽管IRR和trkA受体之间关系的功能性质尚不清楚,但它们在排卵前在卵巢中协调表达的显著时间和空间特异性表明,它们针对与排卵过程相关的一系列功能相关的下游事件。
The insulin receptor-related receptor (IRR) is a member of the insulin receptor family that, on its own, recognizes neither insulin nor any of the identified insulin-related peptides. In both the nervous system and peripheral tissues, IRR mRNA is detected in cells that also express trkA, the nerve growth factor tyrosine kinase receptor. In the ovary, the trkA gene is transiently activated in thecal-interstitial cells of large antral follicles at the time of the preovulatory surge of gonadotropins. The present study shows that the IRR gene is expressed in the same ovarian compartment, that IRR mRNA content increases strikingly in these cells in the afternoon of the first proestrus, and that-as in the case of trkA mRNA-the increase is caused by gonadotropins. The IRR mRNA species primarily affected is that encoding the full-length receptor; its increased abundance was accompanied by a corresponding change in IRR protein content. An extensive molecular search using several approaches, including the screening of cDNA libraries and PCR amplification with degenerate primers, did not yield an IRR ligand. Phylogenetic analysis of 20 insulin-related sequences and 15 relaxin family peptides from selected vertebrates indicated that the mammalian genome is unlikely to contain an additional ligand expressed from a distinct gene that is closely related to the insulin family. Although the functional nature of the relationship between IRR and trkA receptors is unknown, the remarkable temporal and spatial specificities of their coordinated expression in the ovary before ovulation suggests that they target a functionally related set of downstream events associated with the ovulatory process.