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Journal of the American Academy of Dermatology
Volume 58, n° 2
pages 238-250 (février 2008)
Doi : 10.1016/j.jaad.2007.10.014

Expression patterns of the glial cell line–derived neurotrophic factor, neurturin, their cognate receptors GFR⍺-1, GFR⍺-2, and a common signal transduction element c-Ret in the human skin hair follicles

Mohamed A. Adly, PhD a, Hanan A. Assaf, MD b, Paolo Pertile c, Mahmoud R. Hussein, MSc, MD, PhD, MRCPath, EBP d, , Ralf Paus, MD e
a Department of Zoology, Faculty of Science, Sohag University, Sohag, Egypt 
b Department of Dermatology and Venereology, Faculty of Medicine, Sohag University, Sohag, Egypt 
c Cutech Srl, Padova, Italy 
d Department of Pathology, Faculty of Medicine, Assuit University, Assuit, Egypt 
e Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany 

Reprint requests: Mahmoud R. Hussein, MSc, MD, PhD, MRCPath, EBP, Department of Pathology, Faculty of Medicine, Assuit University Hospitals, Assuit University, Assuit, Egypt.

Glial cell line–derived neurotrophic factor (GDNF) and a related family member, neurturin (NTN), and their cognate receptors (GFR⍺-1 and GFR⍺-2, for GDNF and NTN, respectively) are distal members of the transforming growth factor-β superfamily. They are involved in the control of murine hair follicle (HF) cycling. This study tests the hypothesis that GDNF and NTN, and their cognate receptors, are expressed in the human HF and their expression varies in the different stages of the HF cycle.


The expression pattern of these proteins was examined in human HF by immunofluorescence, immunoalkalinephosphatase staining methods, and reverse transcription-polymerase chain reaction (GDNF). The functional effects (GDNF and NTN) were examined in organ culture of the microdissected HFs.


GDNF, NTN, GFR⍺-1, GFR⍺-2, and c-Ret proteins were weakly expressed in catagen and telogen HFs. In contrast, they were strongly expressed in the epithelial and mesenchymal compartments of the anagen HF. GDNF gene was transcribed, both in the human scalp skin and in the isolated anagen HFs (reverse transcription-polymerase chain reaction). In HF organ culture, GDNF (but not NTN) increased the number of the proliferating HF keratinocytes (Ki 67 + cells). GDNF partially protected HFs from transforming growth factor-β2–induced premature catagen transition.




GDNF, NTN, GFR⍺-1, GFR⍺-2, and c-Ret proteins are differentially expressed in the different stages of HF cycle. GFR⍺-mediated signaling involves c-Ret and may play a role in human HF biology.

The full text of this article is available in PDF format.

Abbreviations used : CTS, DP, GDNF, HF, IR, IRS, NTN, ORS, PCR, RT, TBS, TGF

 Supported in part by grants from Deutsche Forschungsgemeinschaft (DFG Pa 345/6-4) and Cutech Srl to Dr Paus.
 Conflicts of interest: None declared.

© 2008  American Academy of Dermatology, Inc.@@#104156@@
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