Epidermal growth factor as a biologic switch in hair growth cycle.
The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis. Data from immunoprecipitation and immunoblotting showed that epidermal growth factor signals through EGFR/ErbB2 heterodimers in skin. Furthermore, topical application of tyrphostin AG1478 or AG825, specific inhibitors of EGFR and ErbB2, respectively, completely inhibited new hair growth in wild type mice but not in transgenic mice. When the transgenic mice were crossed with waved-2 mice, which possess a lower kinase activity of EGFR, the hair phenotype was rescued in the offspring. Taken together, these data suggest that EGFR signaling is indispensable for the initiation of hair growth. On the other hand, continuous expression of epidermal growth factor prevents entry into the catagen phase. We propose that epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle, guarding the entry to and exit from the anagen phase.
Mak
Kingston K L
KK
Department of Paediatrics and Adolescent Medicine, the University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong.
Chan
Siu Yuen
SY
D000818:Animals; D002455:Cell Division; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006197:Hair / Q000378:metabolism; D018859:Hair Follicle / Q000502:physiology; D006579:Heterozygote; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010641:Phenotype; D010766:Phosphorylation; D011233:Precipitin Tests; D011799:Quinazolines; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012879:Skin Physiological Phenomena; D013997:Time Factors; D020032:Tyrphostins / Q000494:pharmacology
D008024:Ligands; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor