Epidermal growth factor delays the development of the epidermis and hair follicles of mice during growth of the first coat

Abstract

The structure of the epidermis and hair-follicle bulbs and the proliferative activities of their component cells were studied in the midside skin of male mice treated with epidermal growth factor (EGF) or saline during formation of the first coat (days 0-21). The epidermis was thickest at birth, but in control animals became progressively thinner as cell size and the number of layers of granular and cornified cells were reduced. EGF treatment from birth resulted in a thickening of the epidermis at 5 days of age, and at 5 and 8 days the histological appearance was strikingly similar to that on the day of birth. At 12 and 21 days the structure of the epidermis of EGF-treated mice more closely resembled that of contemporaneous controls. The mitotic and labeling indices of the basal cells of control epidermis declined throughout the sampling period from peak values on the day of birth. By contrast, these indices were maintained at birth levels in EGF-treated mice for 8 days before declining to approximate those of controls at 12 and 21 days.Hair growth rate was inhibited and hair diameter reduced in EGF-treated mice (Moore et al., 1981a). These observations were reflected in changes in the follicle bulb. Both the growth of the bulb and the increase in numbers of bulb cells observed during the early part of the anagen phase were inhibited by EGF. However, neither the size of the dermal papilla nor the numbers of papilla cells were significantly altered in treated animals. The mitotic index of the bulb cell population declined during the sampling period in both experimental and control groups. However, the labeling index of bulb cells of EGF-treated mice was significantly increased over contemporaneous control values on days 8 and 12. Rather than stimulating epidermal growth during the early postnatal period, these observations indicate that EGF delays the normal process of skin development by maintaining the proliferative and differentiation processes active in the cell populations at the time of birth. As a consequence of this, follicle development and hair growth are inhibited. Levi-Montalcini and Cohen (1960) and Cohen and Elliott (1963) reported that a submaxillary gland protein, epidermal growth factor (EGF), promoted the keratinization of cells of the epidermis when administered to mice after birth, but inhibited hair growth. The apparent discrepancy between the responses of the cells of the epidermis on one hand and those of the epidermal derivatives, the hair follicles, on the other, has not been studied in any detail. Recently, we examined one aspect of this in a study of the monotrichs of the first hair coat in mice. Daily injections of EGF from birth resulted in the development of curved fibers and caused a retardation of length growth rate and a reduction in hair diameter (Moore et al., 1981a). In this report we have compared the morphology and proliferative activities of cell populations of the epidermis and hair-follicle bulbs in EGF-treated and control mice during the growth of the hair coat, wh...

The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase.

“…Nimierous reports describe the sensitivity of skin and hair to exogenous EGFR ligands (Moore et al 1983;Tam 1985;Barrandon and Green 1987;Vassar and Fuchs 1991). Our demonstration that EGFR transcripts are localized to the outer root sheath of hair follicles is consistent with a previous assay of receptor protein (Green et al 1984;King et al 1990).…”

Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle

“…The present study showed that even when EGF was overexpressed, the skin histology was normal at birth. By Day 4, there was an increase in epidermal thickness but a decrease in both overall skin thickness and hair follicle diameter, consistent with earlier studies that involved the injection of EGF into newborn animals and showed an inhibitory role of EGF in skin development (2,3). It has also been shown that although EGFR is expressed continuously in the epidermis, expression in the hair follicles started a few days after birth.…”

“…However, the delay in skin development was not prolonged, and the mitotic index and thickness of the epidermis declined to that of control values a few days later. By Day 41, final hair length and diameter were not significantly reduced (3). EGF also had no effect on back skin when injected into mice with ages ranging from 12 to 20 days (2).…”

“…EGF also had no effect on back skin when injected into mice with ages ranging from 12 to 20 days (2). The authors suggested that EGF was only active in skin during the neonatal period (3). In contrast, EGF induces follicle regression besides inhibiting hair fiber production and stimulating mitosis of the basal epidermal cells when infused into adult sheep (4).…”

Neu differentiation factor upregulates epidermal migration and integrin expression in excisional wounds.

“…These epidermal effects contrast those described for two other members of the EGF family, EGF and TGF-a, both of which induce marked keratinocyte proliferation but do not stimulate normal keratinocyte differentiation (38,39). In addition, both EGF and TGF-a inhibit the growth of hair follicles (40,41), while EGF stimulates the growth of sebaceous (42) and sweat glands (43). In contrast, rhNDF-a2 has no apparent effect on any dermal adnexa, both in the rabbit ear excisional wound model and after systemic administration to neonatal rats (Danilenko, D. M., and G. F. Pierce, unpublished data).…”