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PMID: 9736028 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A new role for neurotrophin-3: involvement in the regulation of hair follicle regression (catagen).

The American journal of pathology ·Vol. 153 ·No. 3 ·1998-09-00 ·Pages 785-99

Botchkarev VA, Welker P, Albers KM, Botchkareva NV, Metz M, Lewin GR, Bulfone-Paus S, Peters EM, Lindner G, Paus R

Abstract

Nervous system and hair follicle epithelium share a common ectodermal origin, and some neurotrophins (NTs) can modulate keratinocyte proliferation and apoptosis. Therefore, it is reasonable to ask whether NTs are also involved in hair growth control. Here, we show that the expression of NT-3 and its high-affinity receptor, tyrosine kinase C, in the skin of C57BL/6 mice is strikingly hair cycle-dependent, with maximal transcript and protein expression seen during spontaneous hair follicle regression (catagen). During catagen, NT-3 and tyrosine kinase C are co-expressed by terminal deoxynucleotidyl transferase-mediated in situ nick end labeling-positive keratinocytes in the club hair and secondary germ. NT-3-overexpressing transgenic mice show precocious catagen development during the postnatal initiation of hair follicle cycling, whereas heterozygous NT-3 knockout (+/-) mice display a significant catagen retardation. Finally, NT-3 stimulates catagen development in organ culture of normal C57BL/6 mouse skin. These observations suggest that the hair follicle is both a source and target of NT-3 and that NT-3/tyrosine kinase C signaling is functionally important in the control of hair follicle regression. Therefore, tyrosine kinase C agonists and antagonists deserve systematic exploration for the management of hair growth disorders that are related to premature (alopecia/effluvium) or retarded catagen (hirsutism/hypertrichosis).

MeSH Terms
Animals Apoptosis DNA Primers/chemistry Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique, Indirect Gene Expression Regulation/physiology Hair Follicle/cytology,drug effects,physiology Keratinocytes/cytology,metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nerve Growth Factors/genetics,physiology Neurotrophin 3 Organ Culture Techniques Polymerase Chain Reaction Receptor Protein-Tyrosine Kinases/genetics,metabolism Receptor, Nerve Growth Factor Receptor, trkC Receptors, Nerve Growth Factor/genetics,metabolism Skin/cytology,metabolism
Chemicals
DNA Primers Nerve Growth Factors Neurotrophin 3 Receptor, Nerve Growth Factor Receptors, Nerve Growth Factor Receptor Protein-Tyrosine Kinases Receptor, trkC
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Botchkarev V A
Department of Dermatology, Charité Hospital, Humboldt University, Berlin, Germany.
Welker P
Albers K M
Botchkareva N V
Metz M
Lewin G R
Bulfone-Paus S
Peters E M
Lindner G
Paus R
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65621-0
Published
1998-09-00
Pages
785-99
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1853006
Subset
IM
Grants
NINDS NIH HHS · R01 NS031826 · United States
NINDS NIH HHS · R01 NS033730 · United States
NINDS NIH HHS · R01 NS 33730 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65621-0 PMC Full Text View journal details
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