Testicular Synthesis and Vitamin D Action

Testicular Synthesis and Vitamin D Action
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DOI:
10.1210/jc.2014-1690
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发表时间:
2014-10-01
影响因子:
5.8
通讯作者:
Obermayer-Pietsch, B.
Obermayer-Pietsch, B.
中科院分区:
医学2区
文献类型:
--
作者:
Hofer, D.;Muenzker, J.;Obermayer-Pietsch, B.

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背景:维生素 D 系统不仅在骨代谢中具有多效作用。它在睾丸类固醇生成中的作用是新的,值得深入研究。目的:我们假设维生素 D,尤其是 1,25 二羟基维生素 D-3 [1,25(OH)(2)D-3(骨化三醇)] 诱导男性类固醇生成,并打算确定其对睾丸雄激素调节中的基因和途径的影响。方法:人成人原代睾丸细胞 分离并用 1,25(OH)(2)D-3 处理,并通过微阵列分析分析其基因表达水平。通过实时定量PCR证实了高度调控的基因。此外,还评估了1,25(OH)(2)D-3与LH和IGF-I组合对雄激素基因表达水平的影响。培养基中的 T 水平通过高分辨率 ELISA 测定。使用免疫细胞化学在基线和 1,25(OH)(2)D-3 刺激后确认了维生素 D 受体的表达。结果:微阵列描绘了 63 个受 1,25(OH)(2)D-3 显着调节的基因,包括与男性雄激素和维生素 D 代谢相关的基因,主要由维生素 D 受体/类视黄醇 X 受体激活触发。 1,25(OH) 2D3 导致人类睾丸细胞培养物中生殖基因表达谱的显着变化,并显着增加 T 合成。结论:来自我们的人类原代睾丸细胞培养模型的数据表明,维生素 D 在体外男性类固醇生成中发挥着重要作用。
Context: The vitamin D system has pleiotropic effects not only in bone metabolism. Its role in testicular steroidogenesis is new and deserves intensive research.Objective: We hypothesize that vitamin D, especially 1,25 dihydroxyvitamin D-3 [1,25(OH)(2)D-3 (calcitriol)] induces male steroidogenesis and intend to identify its impact on genes and pathways in testicular androgen regulation.Methods: Human adult primary testicular cells were isolated, treated with 1,25(OH)(2)D-3, and their gene expression levels profiled by microarray analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In addition, the effects of 1,25(OH)(2)D-3 in combination with LH and IGF-I on the gene expression level of androgens were assessed. T levels in the culture media were determined by a high-resolution ELISA. The expression of vitamin D receptor was confirmed at baseline and after 1,25(OH)(2)D-3 stimulation using immunocytochemistry.Results: Microarrays depicted 63 genes significantly regulated by 1,25(OH)(2)D-3, including genes related to male androgen and vitamin D metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor activation. 1,25(OH) 2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased T synthesis in human testicular cell cultures.Conclusions: Data from our human primary testicular cell culture model suggest that vitamin D plays a major role in male steroidogenesis in vitro.