A. Catizone et al., Expression and functional role of hepatocyte growth factor receptor (C-MET) during postnatal rat testis development, ENDOCRINOL, 142(5), 2001, pp. 1828-1834
The met protooncogene encodes the hepatocyte growth factor receptor (HGFR,
c-met). C-met, a tyrosine kinase receptor protein, is widely expressed in d
ifferent cell types including the male reproductive tract. As we recently d
emonstrated, both c-met messenger RNA and protein are expressed in prebuber
al rat testis. The aim of this work was to detect the expression of c-met d
uring postnatal testis development and to study its functional role. Our fi
ndings show that in total rat testis e-met is expressed during postnatal li
fe until the sexual maturation of the animals. To evaluate the receptor exp
ression in the different cell types in the testis, homogeneous cell populat
ions of Sertoli and peritubular myoid cells were isolated from the seminife
rous tubules of 10- and 35-day-old animals. c-met gene is expressed in myoi
d 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 immunocytoch
emistry and its expression correlates with gene expression. The receptor is
functionally active because HGF administration induces morphological chang
es in myoid cells and in c-met-expressing Sertoli cells. As a consequence o
f HGF addition, Sertoli cells cultured on reconstituted basement membrane r
eorganize into cord-like structures that resemble testicular seminiferous c
ords. The data here reported demonstrate for the first: time that in Sertol
i cells c-met expression is developmentally regulated being present and fun
ctionally active in postpuberal Sertoli cells. Given that c-met expression
persists in myoid cells during postnatal testis development and that in Ser
toli cells its expression correlates over time with germ cell differentiati
on and lumen formation, we conclude that the c-met/HGF system is involved i
n testis development and function.