Induction of Endothelin-2 Expression by Luteinizing Hormone and Hypoxia: Possible Role in Bovine Corpus Luteum Formation
Induction of Endothelin-2 Expression by Luteinizing Hormone and Hypoxia: Possible Role in Bovine Corpus Luteum Formation
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DOI：
10.1210/en.2009-0767
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Meidan, Rina
中科院分区：
文献类型：
--
作者：
Klipper, Eyal;Levit, Anat;Meidan, Rina
研究了内皮素 - 2（EDN2）表达的模式和调控及其在牛卵巢中的可能作用。在体内测定了黄体（CL）中以及促性腺激素释放激素（GnRH）诱导的卵泡 - 黄体转化过程中内皮素 - 2 mRNA的表达。内皮素 - 2仅在早期黄体中升高，在较晚期黄体中不存在。在早期黄体中，内皮素 - 2 mRNA主要在黄体细胞中被检测到，而不在表达内皮素 - 1基因的内皮细胞中。类似地，在排卵前卵泡中，内皮素 - 2在颗粒细胞（GCs）中表达，而不在血管化的内膜细胞中表达。促黄体生成素（LH）和缺氧是黄体形成的两种主要刺激因素。因此，在缺氧条件下用牛促黄体生成素培养颗粒细胞。用牛促黄体生成素培养的颗粒细胞在42小时后内皮素 - 2 mRNA增加。氯化钴（CoCl₂），一种模拟缺氧的试剂，以剂量依赖的方式提高颗粒细胞中的内皮素 - 2。在低氧张力（1%）下培养人颗粒细胞系（猿猴病毒40大T抗原）在6小时和24小时后内皮素 - 2增加。在这两种细胞类型中，随着内皮素 - 2的增加，缺氧也增加了血管内皮生长因子。内皮素 - 2诱导颗粒细胞发生变化，这些变化是发育中的黄体的特征：细胞增殖以及血管内皮生长因子和环氧合酶 - 2（mRNA和蛋白质水平）的上调。人绒毛膜促性腺激素也上调这两个基因。靶向内皮素转化酶 - 1的小干扰RNA有效地降低了其mRNA水平。这种预期会降低成熟内皮素 - 2肽产生的处理，抑制了血管内皮生长因子mRNA水平和颗粒细胞数量。总之，这些数据表明，在牛早期黄体中由促黄体生成素峰和缺氧引发的内皮素 - 2升高，可能通过促进血管生成、细胞增殖和分化来促进黄体形成。（《内分泌学》151: 1914 - 1922, 2010）
The pattern and regulation of endothlin-2 (EDN2) expression and its putative roles in bovine ovaries were investigated. EDN2 mRNA was determined in corpus luteum ( CL) and during folliculoluteal transition induced by GnRH in vivo. EDN2 was elevated only in the early CL and was not present in older CL. In the young CL, EDN2 mRNA was identified mainly in luteal cells but not endothelial cells that expressed the EDN1 gene. Similarly, in preovulatory follicles, EDN2 was expressed in the granulosa cells (GCs) and not in the vascular theca interna. LH and hypoxia are two major stimulants of CL formation. Therefore, GCs were cultured with bovine LH, under hypoxic conditions. GCs incubated with bovine LH resulted in increased EDN2 mRNA 42 h later. CoCl2, a hypoxia-mimicking agent, elevated EDN2 in GCs in a dose-dependent manner. Incubation of the human GC line ( Simian virus 40 large T antigen) under low oxygen tension (1%) augmented EDN2 6 and 24 h later. In these two cell types, along with EDN2, hypoxia augmented VEGF. EDN2 induced in GCs changes that characterize the developing CL: cell proliferation as well as up-regulation of vascular endothelial growth factor and cyclooxygenase-2 ( mRNA and protein levels). Human chorionic gonadotropin also up-regulated these two genes. Small interfering RNA targeting EDN-converting enzyme-1 effectively reduced its mRNA levels. This treatment, expected to lower the mature EDN2 peptide production, inhibited VEGF mRNA levels and GC numbers. Together these data suggest that elevated EDN2 in the early bovine CL, triggered by LH surge and hypoxia, may facilitate CL formation by promoting angiogenesis, cell proliferation, and differentiation. (Endocrinology 151: 1914-1922, 2010)