Leptin secretion by human ejaculated spermatozoa
Leptin secretion by human ejaculated spermatozoa
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DOI：
10.1210/jc.2004-2233
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Andò, S
中科院分区：
文献类型：
--
作者：
Aquila, S;Gentile, M;Andò, S
简介：瘦素的作用是一个动态的调查领域，继续扩大超出最初设想的基本脂肪抑制模型。在这里，我们表明，瘦素的表达和分泌从人类射精spermatozoes.Methods：通过RT-PCR，Western blot和免疫荧光技术，我们已经证明，人精子表达瘦素。放射免疫分析法（RIA）显示瘦素分泌。采用磷脂酰肌醇激酶-3（PI 3 K）活性测定和Western blot检测PI 3 K/Akt通路。结果：获能精子与未获能精子的瘦素分泌量存在较大差异，提示瘦素在获能过程中起重要作用。事实上，在未获能的精子中，瘦素增强胆固醇流出和蛋白酪氨酸磷酸化。在未获能的精子中，胰岛素和瘦素均增加PI 3 K活性、Akt S473和糖原合成酶激酶-3 S9磷酸化。有趣的是，在获能过程中，伴随着两种激素的大量释放，我们观察到糖原合成酶激酶-3 S9的磷酸化强烈减少，该激酶位于调节糖原合成酶的Akt下游。我们的结果从GSA表明，酶的活性显着高于获能的精子在未获能。特别是，在uncapacitated精子，GSA似乎取决于激素的浓度，因为酶的活性在低剂量刺激，而它在高剂量抑制。此外，瘦素和胰岛素均以自分泌方式调节精子糖原的合成。结论：精子分泌瘦素表明，雄配子可能通过系统性瘦素独立调节自身代谢。这些数据开启了关于瘦素在男性生育中的重要性的新思考。
Introduction: Leptin action is a dynamic area of investigation that continues to broaden beyond the basic lipostatic model originally envisaged. Here, we show that leptin is expressed in and secreted from human ejaculated spermatozoa.Methods: By RT-PCR, Western blot, and immunofluorescence techniques, we have demonstrated that human sperm express leptin. RIA method evidenced leptin secretion. Phosphatidyl-inositol-kinase-3 (PI3K)/Akt pathway was examined by PI3K activity assay and Western blot. Leptin and insulin regulation of glycogen synthesis was evaluated by glycogen synthase activity (GSA).Results: The large differences of leptin secretion between uncapacitated and capacitated sperm suggest a functional role for leptin in capacitation. Indeed, in uncapacitated sperm, leptin enhances both cholesterol efflux and protein tyrosine phosphorylation. In uncapacitated sperm, both insulin and leptin increased PI3K activity, Akt S473, and glycogen synthase kinase-3 S9 phosphorylation. Interestingly, during capacitation, concomitantly to the massive release of both hormones, we observed a strong reduction in the phosphorylation of glycogen synthase kinase-3 S9, kinase downstream of Akt that regulates the glycogen synthase. Our results from GSA showed that the enzymatic activity was significantly higher in uncapacitated than in capacitated sperm. Particularly, in uncapacitated sperm, GSA appeared to depend on the hormones concentration, because the enzymatic activity was stimulated at low doses, whereas it was inhibited at high doses. Moreover, both leptin and insulin regulate in autocrine fashion sperm glycogen synthesis.Conclusion: Leptin secretion by sperm suggests that the male gamete may be able to modulate its metabolism independently by systemic leptin. These data open new considerations about leptin significance in male fertility.