Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India.
Andrologia. 2012 May;44 Suppl 1:615-20. doi: 10.1111/j.1439-0272.2011.01239.x. Epub 2011 Nov 2.
Mammalian testis functions at a temperature and oxygen tension (pO(2)) lower than the core body. Hypoxia-inducible factor-1α (HIF-1α) mediates the adaptive responses to hypoxia such as production of angiogenic vascular endothelial growth factor (VEGF) in a variety of cells and tissues. VEGF production in Leydig cells is stimulated by luteinising hormone (LH)/cAMP. We have conducted experiments to find out whether HIF-1α is involved in LH/cAMP-induced secretion of VEGF by Leydig cell-derived MA-10 cells. Both cobalt chloride (CoCl(2)), an inducer of hypoxia, and 8-Br-cAMP enhanced HIF-1α activity followed by an increase in VEGF secretion. However, there was no change in mRNA levels of HIF-1α. Inhibition of HIF-1α activity by cyclosporine A (CsA) inhibited a rise in VEGF production in response to CoCl(2) as well as 8-Br-cAMP. Inhibitors of protein kinase A (PKA), extracellular regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3 kinase/Akt (PI3-K/Akt) inhibited the increase in VEGF levels in response to both CoCl(2) and 8-Br-cAMP. The data suggest that HIF-1α is a mediator of hypoxia- as well as 8-Br-cAMP-stimulated production of VEGF in MA-10 cells; both the stimuli act through a common signalling cascade.
哺乳动物的睾丸在温度和氧气张力（pO(2)）低于核心体温的环境下发挥作用。缺氧诱导因子-1α（HIF-1α）介导了多种细胞和组织对缺氧的适应性反应，如血管内皮生长因子（VEGF）的产生。黄体生成素（LH）/cAMP 刺激间质细胞产生 VEGF。我们进行了实验以确定 HIF-1α 是否参与 LH/cAMP 诱导的间质细胞衍生的 MA-10 细胞中 VEGF 的分泌。氯化钴（CoCl(2)）作为缺氧诱导剂和 8-Br-cAMP 均增强了 HIF-1α 的活性，随后 VEGF 分泌增加。然而，HIF-1α 的 mRNA 水平没有变化。环孢素 A（CsA）抑制 HIF-1α 活性可抑制 CoCl(2)和 8-Br-cAMP 诱导的 VEGF 产生增加。蛋白激酶 A（PKA）、细胞外调节激酶 1/2（ERK1/2）和磷脂酰肌醇-3 激酶/蛋白激酶 B（PI3-K/Akt）抑制剂均可抑制 CoCl(2)和 8-Br-cAMP 诱导的 VEGF 水平升高。数据表明，HIF-1α 是 MA-10 细胞中缺氧以及 8-Br-cAMP 刺激 VEGF 产生的介质；两种刺激均通过共同的信号级联起作用。
