Nv. Botchkareva et al., New roles for glial cell line-derived neurotrophic factor and neurturin - Involvement in hair cycle control, AM J PATH, 156(3), 2000, pp. 1041-1053
Citations number
78
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), and th
eir receptors, GDNF family receptor alpha-1. (GFR alpha-1) and GDNF family
receptor alpha-2 (GFR alpha-2), are critically important for kidney and ner
vous system development. However, their role in skin biology, specifically
in hair growth control, is as yet unknown. We have studied expression and f
unction of GDNF, neurturin, GFR alpha-1, and GFR alpha-2 in murine skin dur
ing the cyclic transformation of the hair follicle (HF) from its resting st
ate (telogen) to active growth (anagen) and then through regression (catage
n) back to telogen. GDNF protein and GFR alpha-1 messenger RNA are prominen
tly expressed in telogen skin, which lacks NTN and GFR alpha-2 transcripts.
Early anagen development is accompanied by a significant decline in the sk
in content of GDNF protein and GFR alpha-1 transcripts. During the anagen-c
atagen transition, GDNF, GFR alpha-1, NTN, and GFR alpha-2 transcripts reac
h maximal levels. Compared with wild-type controls, GFR alpha-1 (+/-) and G
FR alpha-2 (-/-) knockout mice show a significantly accelerated catagen dev
elopment. Furthermore, GDNF or NTN administration significantly retards HF
regression in organ-cultured mouse skin. This suggests important, previousl
y unrecognized roles for GDNF/GFR alpha-1 and NTN/GFR alpha-2 signaling in
skin biology, specifically in the control of apoptosis-driven HF involution
, and raises the possibility that GFR alpha-1/GFR alpha-2 agonists/antagoni
sts might become exploitable for the treatment of hair growth disorders tha
t are related to abnormalities in catagen development.