Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle

Abstract

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.

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

“…Constitutive expression of EGF inhibits transition from anagen to catagen (51). The earliest change in gene expression in the back skin of Fa2h Ϫ/Ϫ mice was the strong up-regulation of Epgn in the basal layer of the SG and in some adjacent cells of the ORS.…”

“…FA2H Deficiency Causes Hyperproliferation of Sebocytes-EGF receptor/ErbB2 signaling appears to be essential for hair growth, and EGF signaling is turned off during anagen to catagen transition (51). Constitutive expression of EGF inhibits transition from anagen to catagen (51).…”

Erlotinib-induced Adverse Skin Reactions

“…Prolonged eyebrow, curly hairs, and even the darkening of the hair may be simultaneously seen in a single individual [31]. EGF-R plays a role in the regulation of hair growth cycles, as a switch to begin and end the anagen phase of the hair cycle [32]. It is also suggested that hair growth speed is different depending on different location, such as hair, cheek, ear, eye, and trunk.…”

Gagamyeonryunggobon-dan(Jiājiǎnyánlínggùběn-dān) induces hair regrowth effect from activating hair follicle

“…VEGF in dermal papilla of hair follicle is secreted during telogen while making hair follicle get into new anagen for activating angiogenesis [29][30][31][32][33] .…”

“…Especially during telogen, hair follicle secretes VEGF to activate angiogenesis that makes new anagen come up [29][30][31][32][33] . If anagen is shortened and telogen hairs are increasing, alopecia arises while new growing hairs are decreasing and lost hairs are increasing 34,35) .…”