Melatonin in testes of infertile men: evidence for anti‐proliferative and anti‐oxidant effects on local macrophage and mast cell populations

Melatonin in testes of infertile men: evidence for anti‐proliferative and anti‐oxidant effects on local macrophage and mast cell populations
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不育男性测试中的褪黑激素:对局部巨噬细胞和肥大细胞群的抗增殖和抗氧化作用的证据

DOI:
10.1111/j.2047-2927.2014.00207.x
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发表时间:
2014
期刊:
影响因子:
4.5
通讯作者:
Frungieri MB
Frungieri MB
中科院分区:
医学2区
文献类型:
--
作者:
Rossi SP;Windschuettl S;Matzkin ME;Terradas C;Ponzio R;Puigdomenech E;Levalle O;Calandra RS;Mayerhofer A;Frungieri MB

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褪黑激素通过下丘脑和垂体调节睾丸功能。此外,最近有人提出褪黑激素在睾丸水平的直接作用。我们已经描述了褪黑激素通过褪黑激素亚型1a(mel 1a)受体和局部促肾上腺皮质激素释放激素(CRH)系统抑制仓鼠Leydig细胞中雄激素的产生。褪黑激素/CRH信号通路的初始事件也已建立。褪黑激素和褪黑激素能/CRH系统的所有组件也检测到不育男性的Leydig细胞。本研究试图寻找褪黑素在人睾丸中的其他靶点,并研究褪黑素对这些新靶细胞增殖和氧化状态的影响。为此,对患有精子生成不足或仅支持细胞综合征的患者的人睾丸活检进行评价,并进行细胞培养研究。在人睾丸巨噬细胞(MACs)和肥大细胞(MCs)中发现了褪黑激素受体。在特发性不孕症患者的活检组织中,褪黑激素睾丸浓度与每平方毫米MAC数和TNFα、IL 1 β和COX 2表达呈负相关,但与抗氧化酶SOD 1、过氧化物氧还蛋白1和过氧化氢酶的表达呈正相关。褪黑激素抑制人非睾丸THP-1 MAC细胞系和仓鼠睾丸MAC原代细胞培养物中的增殖以及促炎细胞因子和环氧合酶2(COX 2)的表达。在人HMC-1 MC系中,褪黑激素增加抗氧化酶的表达并减少活性氧(ROS)的产生。结果揭示了褪黑激素的新睾丸靶点,并描述了这种激素对睾丸MAC的抗增殖和抗炎作用。此外,褪黑激素可能对睾丸MC的氧化应激提供保护作用。
Melatonin acting through the hypothalamus and pituitary regulates testicular function. In addition, direct actions of melatonin at the testicular level have been recently suggested. We have described that melatonin inhibits androgen production in hamster Leydig cells via melatonin subtype 1a (mel1a) receptors and the local corticotrophin‐releasing hormone (CRH) system. The initial events of the melatonin/CRH signalling pathway have also been established. Melatonin and all components of the melatonergic/CRH system were also detected in Leydig cells of infertile men. This study attempted to search for additional targets of melatonin in the human testis, and to investigate the effects of melatonin on proliferation and the oxidative state in these novel target cells. To this aim, evaluation of human testicular biopsies of patients suffering from hypospermatogenesis or Sertoli cell only syndrome and cell culture studies were performed. Melatonergic receptors were found in macrophages (MACs) and mast cells (MCs) of the human testis. In biopsies of patients suffering idiopathic infertility, melatonin testicular concentrations were negatively correlated with MAC number per mm2and TNFα, IL1β and COX2 expression, but positively correlated with the expression of the anti‐oxidant enzymes SOD1, peroxiredoxin 1 and catalase. Melatonin inhibited proliferation and the expression of pro‐inflammatory cytokines and cyclooxygenase 2 (COX2) in both the human non‐testicular THP‐1 MAC cell line and primary cell cultures of hamster testicular MACs. In the human HMC‐1 MC line, melatonin increased the expression of anti‐oxidant enzymes and decreased reactive oxygen species (ROS) generation. The results reveal new testicular targets of melatonin and describe anti‐proliferative and anti‐inflammatory effects of this hormone on testicular MACs. Furthermore, melatonin might provide protective effects against oxidative stress in testicular MCs.
两种特发性“仅支持细胞”综合征的形态学证据。
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