Catizone A, Ricci G, Galdieri M
Department of Histology and Medical Embryology, University of Rome "La Sapienza," Rome, Italy.
Endocrinology. 2001 May;142(5):1828-34. doi: 10.1210/endo.142.5.8172.
The met protooncogene encodes the hepatocyte growth factor receptor (HGFR, c-met). C-met, a tyrosine kinase receptor protein, is widely expressed in different cell types including the male reproductive tract. As we recently demonstrated, both c-met messenger RNA and protein are expressed in prebuberal rat testis. The aim of this work was to detect the expression of c-met during postnatal testis development and to study its functional role. Our findings show that in total rat testis c-met is expressed during postnatal life until the sexual maturation of the animals. To evaluate the receptor expression in the different cell types in the testis, homogeneous cell populations of Sertoli and peritubular myoid cells were isolated from the seminiferous tubules of 10- and 35-day-old animals. c-met gene is expressed in myoid cells at the ages considered and its expression decreases with increasing age. By contrast, in Sertoli cells c-met expression is first detectable at 25 days of life and its expression increases with the increasing age being well evident at 35 days of age. C-met protein was detected by immunocytochemistry and its expression correlates with gene expression. The receptor is functionally active because HGF administration induces morphological changes in myoid cells and in c-met-expressing Sertoli cells. As a consequence of HGF addition, Sertoli cells cultured on reconstituted basement membrane reorganize into cord-like structures that resemble testicular seminiferous cords. The data here reported demonstrate for the first time that in Sertoli cells c-met expression is developmentally regulated being present and functionally active in postpuberal Sertoli cells. Given that c-met expression persists in myoid cells during postnatal testis development and that in Sertoli cells its expression correlates over time with germ cell differentiation and lumen formation, we conclude that the c-met/HGF system is involved in testis development and function.
原癌基因met编码肝细胞生长因子受体（HGFR，c-met）。c-met是一种酪氨酸激酶受体蛋白，在包括雄性生殖道在内的不同细胞类型中广泛表达。正如我们最近所证明的，c-met信使核糖核酸和蛋白质在青春期前大鼠睾丸中均有表达。这项工作的目的是检测出生后睾丸发育过程中c-met的表达，并研究其功能作用。我们的研究结果表明，在大鼠整个睾丸中，c-met在出生后直至动物性成熟期间均有表达。为了评估睾丸中不同细胞类型的受体表达情况，从10日龄和35日龄动物的生精小管中分离出了支持细胞和睾丸肌样细胞的同质细胞群。在所研究的年龄段，c-met基因在睾丸肌样细胞中表达，且其表达随年龄增长而降低。相比之下，在支持细胞中，c-met表达在出生后25天首次可检测到，且其表达随年龄增长而增加，在35日龄时非常明显。通过免疫细胞化学检测到了c-met蛋白，其表达与基因表达相关。该受体具有功能活性，因为给予肝细胞生长因子会诱导睾丸肌样细胞和表达c-met的支持细胞发生形态变化。添加肝细胞生长因子后，在重组基底膜上培养的支持细胞会重新组织成类似睾丸生精索的索状结构。本文报道的数据首次证明，在支持细胞中，c-met表达受发育调控，在青春期后支持细胞中存在且具有功能活性。鉴于在出生后睾丸发育过程中c-met在睾丸肌样细胞中持续表达，且在支持细胞中其表达随时间与生殖细胞分化和管腔形成相关，我们得出结论，c-met/肝细胞生长因子系统参与睾丸发育和功能。
