Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease.

Glial cell line-derived neurotrophic factor (GDNF) signals through the product of the ret proto-oncogene, which is known to be mutated in Hirschsprung's disease and other conditions with gut dysmotility. The aim of this study was to determine the presence of GDNF and its receptor component (RET) in human adult and developing intestine and to evaluate their distribution pattern in Hirschsprung's disease. GDNF and RET were detected immunohistochemically, and GDNF was quantified by immunoassay in specimens of human adult and fetal colon and Hirschsprung's disease intestine. GDNF-like immunoreactivity was detected in all specimens. Immunostaining of GDNF was restricted to neural fiber-like structures across the gut wall and was similar to staining with markers of glia and Schwann cells. In contrast, RET immunoreactivity was found only in neural cell bodies. GDNF levels determined by immunoassay were higher in muscle than mucosal gut layers, and there was no difference between affected and unaffected segments of Hirschsprung's disease. GDNF is present in adult and fetal human gut, where it may play a neurotrophic role. Its staining pattern suggests that it is localized in glia or Schwann cells. There seems to be no difference of GDNF levels between affected and unaffected intestinal segments in Hirschsprung's disease.