GDNF and RET-gene expression in anterior pituitary-cell types

Glial cell line-derived neurotrophic factor (GDNF) is expressed in many neuronal and non-neuronal tissues during development as well as in adult animals. GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF. Thereafter this complex binds to and activates the tyrosine kinase receptor RET. In this work, for the first time, we have characterized the expression of both GDNF and RET in the anterior pituitary. First of all, RT-PCR analysis, Western blot and immunohistochemistry of the whole anterior pituitary showed that GDNF, GFRalpha1 and RET are expressed in this gland. Following double-immunofluorescence of consecutive sections we found GDNF immunoreactivity in most cell types, and it was most abundant in corticotrophs (55%), LH (59%) and FSH-producing cells (81%). In contrast, while the majority of somatotrophs (87%) were stained for RET, no positive immunostaining could be detected in other cell types. Taken together, this data indicate that gonadotrophs and corticotrophs are the main source of GDNF synthesized in the anterior pituitary and that the somatotrophs appears to be their target cell. This study provides direct morphological evidences that GDNF may well be acting in a paracrine-like fashion in the regulation of somatotroph cell growth and/or cell function.