The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells

The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells
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DOI:
10.1007/s00418-006-0155-8
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发表时间:
2006-08-01
影响因子:
2.3
通讯作者:
Middendorff, Ralf
Middendorff, Ralf
中科院分区:
生物学3区
文献类型:
--
作者:
Mueller, Dieter;Davidoff, Michail S.;Middendorff, Ralf

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先前的研究已经证明了神经营养因子在啮齿类动物发育和成熟睾丸中的局部功能。为了检查这些信号分子是否存在,也可能在人类睾丸中活跃,我们的特点是化学的表达和细胞定位的已知的神经营养因子及其受体在产前睾丸发育过程中,以及在成年人睾丸。获得的结果显示,存在的神经生长因子(NGF),脑源性神经营养因子,神经营养因子3和4,以及神经营养因子受体p75 NTR,TrkA,TrkB和TrkC在睾丸形态发生。这些蛋白质在成年人睾丸中也可检测到,并且它们的局部表达可以通过免疫印迹和RT-PCR分析在很大程度上证实。值得注意的是,Leydig细胞被发现代表胎儿和成人睾丸内的主要神经营养因子/受体表达位点。用小鼠肿瘤Leydig细胞系进行的功能测定显示,NGF暴露增加细胞类固醇产生,表明在分化过程中的作用。这些研究结果支持了先前公认的间质细胞的神经元特征,为神经营养因子在睾丸形态发生和成熟睾丸中的潜在作用提供了额外的证据,并首次证明了间质细胞中神经营养因子诱导的功能活性。
Previous studies have demonstrated local functions for neurotrophins in the developing and mature testis of rodents. To examine whether these signaling molecules are present and also potentially active in the human testis, we characterized immunohistochemically the expression and cellular localization of the known neurotrophins and their receptors during prenatal testicular development as well as in the adult human testis. Results obtained revealed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 and 4, as well as neurotrophin receptors p75 NTR, TrkA, TrkB, and TrkC during testis morphogenesis. These proteins were also detectable in the adult human testis, and their local expression could be confirmed largely by immunoblot and RT-PCR analyses. Remarkably, the Leydig cells were found to represent the predominant neurotrophin/receptor expression sites within both fetal and adult human testes. Functional assays performed with a mouse tumor Leydig cell line revealed that NGF exposure increases cellular steroid production, indicating a role in differentiation processes. These findings support previously-recognized neuronal characteristics of Leydig cells, provide additional evidence for potential roles of neurotrophins during testis morphogenesis and in the mature testis, and demonstrate for the first time a neurotrophin-induced functional activity in Leydig cells.