Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1β
Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1β
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DOI：
10.1385/endo:18:1:33
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发表时间：
2002-06-01
期刊：
影响因子：
3.7
通讯作者：
Buckingham, JC
中科院分区：
文献类型：
--
作者：
Cover, PO;Baanah-Jones, F;Buckingham, JC
膜联蛋白1是下丘脑-垂体轴中糖皮质激素作用的重要介质;然而，很少有人知道它在介导外周内分泌器官中糖皮质激素作用中的作用。因此，我们进行了初步研究，以探讨膜联蛋白1在体外对睾丸分泌睾酮，糖皮质激素和白细胞介素-1 β（IL-1 β）抑制的过程的影响。促黄体生成素（LH）和毛喉素刺激分散的小鼠睾丸细胞在体外释放睾酮。它们的作用在用地塞米松（DEX）预处理的小鼠细胞中降低。同样，用DEX、皮质酮或11-脱氢皮质酮预孵育未处理小鼠的睾丸细胞，可减少LH刺激的睾酮释放，11 β-羟基类固醇脱氢酶抑制剂、大黄酸和甘珀酸也是如此。类固醇的抑制作用由膜联蛋白1（1-188）（ANXA 1（1-188））（稳定的膜联蛋白1类似物）模拟。IL-1 β可显著降低对LH的反应，这一作用可被吲哚美辛（一种非选择性环氧合酶抑制剂）阻断，并与DEX和ANXA 1（1-188）产生叠加效应。这些结果证实了糖皮质激素和IL-1 β抑制LH刺激的小鼠睾丸细胞睾酮释放的报道。他们还表明，第一次，类固醇的影响是模仿annexin 1，并在相反的相互拮抗作用，在神经内分泌系统，IL-1 β和anneAn 1发挥在睾丸中的附加作用。
Annexin 1 is an important mediator of glucocorticoid action in the hypothalamo-pituitary axis; however, little is known of its role in mediating glucocorticoid actions in the peripheral endocrine organs. Accordingly, we have carried out a preliminary study to investigate the effects of annexin 1 in vitro on the testicular secretion of testosterone, a process inhibited by both glucocorticoids and interleukin-1beta (IL-1beta). Luteinizing hormone (LH) and forskolin stimulated the release of testosterone from dispersed murine testicular cells in vitro. Their effects were reduced in cells from mice pretreated with dexamethasone (DEX). Similarly, preincubation of testicular cells from untreated mice with DEX, corticosterone, or 11-dehydrocorticosterone reduced LH-stimulated testosterone release, as did the 11beta-hydroxysteroid dehydrogenase inhibitors, glycyrrhetinic acid and carbenoxolone. The inhibitory actions of the steroids were mimicked by annexin 1(1-188) (ANXA1(1-188)) (a stable annexin 1 analog). IL-1beta produced a marked decrease in the response to LH, which was blocked by indomethacin, a nonselective cyclooxygenase inhibitor and an additive effect with DEX and ANXA1(1-188). These results confirm reports that glucocorticoids and IL-1beta inhibit LH-stimulated testosterone release from mouse testicular cells. They also show, for the first time, that the effects of the steroids are mimicked by annexin 1 and that, in contrast to their mutually antagonistic effects in the neuroendocrine system, IL-1beta and anneAn 1 exert additive actions in the testis.