GLIAL-DERIVED NEUROTROPHIC FACTOR IN HUMAN ADULT AND FETAL INTESTINE AND IN HIRSCHSPRUNGS-DISEASE

Background & Aims: 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 GD NF and its receptor component (RET) in human adult and developing inte stine and to evaluate their distribution pattern in Hirschsprung's dis ease. Methods: GDNF and RET were detected immunohistochemically, and G DNF was quantified by immunoassay in specimens of human adult and feta l colon and Hirschsprung's disease intestine, Results: GDNF-like immun oreactivity 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 contra st, RET immunoreactivity was found only in neural cell bodies. GDNF le vels determined by immunoassay were higher in muscle than mucosal gut layers, and there was no difference between affected and unaffected se gments of Hirschsprung's disease, Conclusions: GDNF is present in adul t and fetal human gut, where it may play a neurotrophic role, Its stai ning pattern suggests that it is localized in glia or Schwann cells, T here seems to be no difference of GDNF levels between affected and una ffected intestinal segments in Hirschsprung's disease.