Pleiotropic Activities of HGF/c-Met System in Testicular Physiology: Paracrine and Endocrine Implications
Pleiotropic Activities of HGF/c-Met System in Testicular Physiology: Paracrine and Endocrine Implications
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HGF/c-Met 系统在睾丸生理学中的多效活性：旁分泌和内分泌影响
DOI：
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发表时间：
2014
影响因子：
5.2
通讯作者：
A. Catizone
中科院分区：
文献类型：
--
作者：
G. Ricci;A. Catizone
在过去的几十年里，越来越多的证据已经报道了关于肝细胞生长因子（HGF）的表达和功能作用的睾丸生理学的不同方面。本综述旨在总结目前关于这一主题的已知内容。从早期胚胎发育到成年，肝细胞生长因子及其受体c-Met在睾丸中清晰可见。这些分子获得不同的分布模式和作用，这取决于发育阶段或所考虑的出生后年龄。HGF作为睾丸功能的旁分泌调节剂，促进上皮-间充质相互作用，即使在其他器官中也是如此。有趣的是，据报道，睾丸HGF甚至作为一种自分泌因子，其受体可能受到青春期变化的内分泌信号的调节：事实上，支持细胞表达的HGF受体受到FSH给药的上调。HGF又能够改变生物体的内分泌状态，能够增加胎儿和成人Leydig细胞的睾酮分泌。此外，c-Met在有丝分裂和减数分裂的雄性生殖细胞以及精子中表达。c-Met在附睾精子头部和尾部精子细胞膜上的分布模式发生变化，HGF能够在体外维持附睾精子活力，表明该生长因子在精子活力获得中的生理作用。精浆中HGF浓度的显著变化在不同的男科疾病中均有报道。总之，这些数据表明，HGF在控制精子发生和精子质量中具有作用，直接作用于雄性生殖细胞，或间接作用于睾丸的管状和间质体细胞。
In the last decades, a growing body of evidence has been reported concerning the expression and functional role of hepatocyte growth factor (HGF) on different aspects of testicular physiology. This review has the aim to summarize what is currently known regarding this topic. From early embryonic development to adult age, HGF and its receptor c-Met appeared to be clearly detectable in the testis. These molecules acquire different distribution patterns and roles depending on the developmental stage or the post-natal age considered. HGF acts as a paracrine modulator of testicular functions promoting the epithelium–mesenchyme cross-talk as described even in other organs. Interestingly, it has been reported that testicular HGF acts even as an autocrine factor and that its receptor might be modulated by endocrine signals that change at puberty: HGF receptor expressed by Sertoli cells, in fact, is up-regulated by FSH administration. HGF is in turn able to modify endocrine state of the organism being able to increase testosterone secretion of both fetal and adult Leydig cells. Moreover, c-Met is expressed in mitotic and meiotic male germ cells as well as in spermatozoa. The distribution pattern of c-Met on sperm cell membrane changes in the caput and cauda epididymal sperms and HGF is able to maintain epididymal sperm motility in vitro suggesting a physiological role of this growth factor in the acquisition of sperm motility. Noteworthy changes in HGF concentration in seminal plasma have been reported in different andrological diseases. All together these data indicate that HGF has a role in the control of spermatogenesis and sperm quality either directly, acting on male germ cells, or indirectly acting on tubular and interstitial somatic cells of the testis.
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