Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism

Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism
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DOI:
10.1186/1477-7827-7-140
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发表时间:
2009-11-30
影响因子:
4.4
通讯作者:
Ando, Sebastiano
Ando, Sebastiano
中科院分区:
医学2区
文献类型:
--
作者:
Aquila, Saveria;Guido, Carmela;Ando, Sebastiano

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背景资料:1 α,25-二羟基维生素D3(1,25(OH)2D 3)是维生素D3的活性代谢物,在组织中的生物学作用与矿物质代谢无关。最近,我们证实了1,25(OH)_2D_3受体在人精子中的超微结构定位。方法和结果:采用RT-PCR、Western blot和免疫荧光技术,证实人精子中存在1,25(OH)_2D_3受体(VDR)。此外,25(OH)D3-1 α-羟化酶,通过Western印迹分析证明,表明在精子中1,25(OH)2D 3是局部产生的,突出了自分泌-旁分泌反应的潜力。1,25(OH)2D 3通过VDR,增加细胞内Ca 2+水平,运动性和顶体酶活性揭示了这种激素在获得可移植性中的意想不到的意义。在精子中,1,25(OH)2D 3通过VDR降低甘油三酯含量,同时增加脂肪酶活性。1,25(OH)2D 3刺激的Akt、MAPK和GSK 3的快速反应表明该开环甾体参与了不同的精子信号转导通路。结论:我们的数据扩展了1,25(OH)2D 3的作用,超出了其传统的生理作用,为治疗男性生殖障碍提供了新的治疗机会。
Background: A wider biological role of 1alpha, 25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested. Recently, we evidenced the ultrastructural localization the 1,25(OH)2D3 receptor in the human sperm. However, the 1,25(OH)2D3 action in human male reproduction has not yet been clarified.Methods and Results: By RT-PCR, Western blot and Immunofluorescence techniques, we demonstrated that human sperm expresses the 1,25(OH)2D3 receptor (VDR). Besides, 25(OH)D3-1 alpha-hydroxylase, evidenced by Western blot analysis, indicated that in sperm 1,25(OH)2D3 is locally produced, highlighting the potential for autocrine-paracrine responses. 1,25(OH)2D3 through VDR, increased intracellular Ca2+ levels, motility and acrosin activity revealing an unexpected significance of this hormone in the acquisition of fertilizing ability. In sperm, 1,25(OH)2D3 through VDR, reduces triglycerides content concomitantly to the increase of lipase activity. Rapid responses stimulated by 1,25(OH)2D3 have been observed on Akt, MAPK and GSK3 implying that this secosteroid is involved in different sperm signalling pathways.Conclusion: Our data extended the role of 1,25(OH)2D3 beyond its conventional physiological actions, paving the way for novel therapeutic opportunities in the treatment of the male reproduction disorders.