Induction of sweat glands by epidermal growth factor in murine X-linked anhidrotic ectodermal dysplasia

Epidermal growth factor (EGF) stimulates the growth of many tissues and inhibits stimulated gastric acid secretion. Its primary tissue of origin in man is still unknown. We used polyclonal anti-human EGF sera in the peroxidase-antiperoxidase immunocytochemical staining technique to identify immunoreactive human EGF (ihEGF) in tissue sections from 29 subjects ranging from fetuses to 63 years in age. In addition to acinar cells in the submandibular salivary glands and cells of Brunner's duodenal glands, previously reported to contain ihEGF, we found ihEGF in most anterior pituitary glycopeptide hormone-secreting cells, in gastric and pyloric gland cells of the stomach, and in bone marrow cells that resembled mononuclear phagocytes in subjects of all ages. The eccrine sweat glands in the skin of adults also contained ihEGF. Cells containing ihEGF were found singly or in clusters in the trachea of the fetus only. No fetal pancreatic islet cells stained, but occasional cells in neonates and a majority of islet cells in older subjects contained ihEGF; there was no constant association with insulin, glucagon, or somatostatin. Only the lactating breast contained ihEGF. In adults, outer adrenomedullary cells contained ihEGF. Intense immunostaining was observed in the renal medulla, apparently limited to the extracellular area between the renal tubules, and increased with age; the cortex was devoid of ihEGF. No ihEGF was detected in posterior pituitary gland, thyroid gland, heart, lung, or liver at any age. An adult prostate contained ihEGF only in an area of local injury, and some primordial follicles from the ovary of a newborn appeared to contain ihEGF. Thus, many tissues appear to synthesize hEGF, which may exert exocrine, endocrine, or paracrine functions in different tissues and at different ages.

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Reduced epidermal growth factor receptor expression in hypohidrotic ectodermal dysplasia and Tabby mice.

Journal of Clinical Investigation ◽

10.1172/jci118689 ◽

1996 ◽

Vol 97 (11) ◽

pp. 2426-2432 ◽

Cited By ~ 27

Author(s):

G A Vargas ◽

E Fantino ◽

C George-Nascimento ◽

J J Gargus ◽

H T Haigler

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Ectodermal Dysplasia ◽

Growth Factor Receptor ◽

Receptor Expression ◽

Hypohidrotic Ectodermal Dysplasia ◽

Epidermal Growth

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In vivo effects of epidermal growth factor on epidermal pattern formation and hair follicle initiation in the marsupial bandicoot Isoodon macrourus

Reproduction Fertility and Development ◽

10.1071/r96118 ◽

1997 ◽

Vol 9 (5) ◽

pp. 493 ◽

Cited By ~ 6

Author(s):

David L. Adelson ◽

David E. Hollis ◽

James C. Merchant ◽

Bronwyn A. Kelley

Keyword(s):

Growth Factor ◽

Pattern Formation ◽

Epidermal Growth Factor ◽

Hair Follicle ◽

Egf Receptor ◽

Transforming Growth Factor ◽

Hair Follicles ◽

Sweat Glands ◽

Epidermal Growth

The extrauterine development of marsupial pouch young (northern brown bandicoot Isoodon macrourus) has facilitated the study of the effects of murine epidermal growth factor (mEGF) on pattern formation in skin. Hair follicle initiation and development, which in the mouse would occur from about Days 13–14 of gestation onward, occurs postnatally. In the present study the effect in vivo of mEGF on developing skin corresponding to mouse gestational ages from Day 13 onward was examined. Subcutaneous injections of mEGF (0· 5, 1 ·0 and 2· 0 µg g-1 body weight) or equivalent volumes of saline (0· 9% w/w) were administered daily, before and during hair follicle initiation and development. Murine EGF inhibited the formation of hair follicles, hair follicle sweat glands, sebaceous glands and dermal papillae. The pattern of follicle initiation was perturbed. The characteristic trio follicle grouping was absent, and follicle rudiment densities (no. per mm2skin surface) were significantly lower in animals treated with mEGF, whereas follicle diameters were increased. These data may reflect a role for the epidermal growth factor (EGF) receptor in epidermal pattern formation. The EGF receptor and its potential ligands (such as EGF, transforming growth factor (TGF-α) or other yet-to-be-discovered ligands) perhaps act as parts of a pattern-forming system in vertebrate skin. Extra keyword: EGF receptor.

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Epidermal growth factor (EGF) affects sulphydryl and disulphide levels in cultured mouse skin : possible relationship between effects of EGF and of the tabby gene on thiols

Biochemistry and Cell Biology ◽

10.1139/o87-087 ◽

1987 ◽

Vol 65 (7) ◽

pp. 658-667 ◽

Cited By ~ 5

Author(s):

Nancy Weeks Robertson ◽

Stan R. Blecher

Keyword(s):

Tissue Culture ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Ectodermal Dysplasia ◽

Mouse Skin ◽

Linked Gene ◽

Epidermal Growth ◽

High Doses ◽

Very High ◽

Wild Type Control

Studies from our laboratory have previously shown that the syndrome produced in the mouse by the X-linked gene tabby (Ta) has many features in common with human X-linked hypohidrotic ectodermal dysplasia. We have also demonstrated that tabby has abnormally elevated epidermal sulphydryl (SH) : disulphide (SS) ratios, in common with an autosomal form of ectodermal dysplasia. The organs and tissues affected in many of the traits of these syndromes are targets of epidermal growth factor (EGF) and we have shown that the EGF-producing cells are deficient in tabby. In the present study we examined whether EGF affects SH and SS levels in normal mouse skin in tissue culture, and we report here that it does. EGF at a concentration of 25 ng/mL tissue culture medium lowers SH levels as compared with controls (0 ng/mL) in the epidermal layers examined (stratum malpighii of the tail and stratum malpighii and stratum corneum of flank skin). In general, other concentrations of EGF increase epidermal SH levels, although very high doses also reduce them. EGF at 25 ng/mL also lowers total SH + SS concentrations in the epidermal layers. Fetuses hemizygous for the Ta gene appear to have higher total SH + SS epidermal concentrations than their wild-type control littermates. These data, taken together with some of our previous findings, suggest the possibility that a relationship may exist between Ta, EGF, and thiol concentrations. Further study is required to elucidate this relationship.

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Effect of the X-linked gene Tabby (Ta) on eyelid opening and incisor eruption in neonatal mice is opposite to that of epidermal growth factor

Development ◽

10.1242/dev.108.2.349 ◽

1990 ◽

Vol 108 (2) ◽

pp. 349-355

Author(s):

J. Kapalanga ◽

S.R. Blecher

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Egf Receptor ◽

Ectodermal Dysplasia ◽

Closed Cycle ◽

Hypohidrotic Ectodermal Dysplasia ◽

Linked Gene ◽

Eyes Closed ◽

Eyes Open ◽

Epidermal Growth

Studies on eyelid opening and incisor eruption in 216 neonatal Tabby (Ta)-bearing mice and wildtype controls (35 Ta/Y, 62 + /Y, 30 Ta/Ta, 57 Ta/+ and 32 +/+) showed that in animals hemizygous and homozygous for Ta, the timing of eyelid opening and incisor eruption was significantly delayed (P less than 0.05). It was also observed that once open, the eyes of mutant pups do not remain open for long but soon close again for several days before reopening. An iterative eyes open-eyes closed process seems to continue beyond puberty. Studies in 25 epidermal growth factor (EGF)-treated mutants and 23 saline-treated controls showed that neonatal EGF injections (4 micrograms g-1 body weight per day) reversed the delayed timing of eyelid opening and incisor eruption in hemizygote and homozygote Tabby mice. However, both mutant and wildtype EGF-treated mice also showed the eyes open-eyes closed cycle, whereas untreated nonmutant mice did not. Because Tabby appears to be genetically homologous to the gene for human X-linked hypohidrotic ectodermal dysplasia, these results may have potential clinical significance. The eyes open-eyes closed cycle may involve cycling levels of EGF receptor; since the gene for this receptor shows homology with an oncogene, this system may be useful in studies on genetic control of oncogene function.

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Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands.

Journal of Histochemistry & Cytochemistry ◽

10.1177/40.2.1552167 ◽

1992 ◽

Vol 40 (2) ◽

pp. 241-249 ◽

Cited By ~ 12

Author(s):

K Saga ◽

M Takahashi

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Immunoelectron Microscopy ◽

Secretory Granules ◽

Myoepithelial Cells ◽

Sweat Glands ◽

Secretory Cells ◽

Epidermal Growth ◽

Eccrine Sweat Glands ◽

Eccrine Sweat

We studied the localization of the epidermal growth factor (EGF) in eccrine and apocrine sweat glands with light microscopic and electron microscopic immunohistochemistry. Anti-human EGF (anti-hEGF) polyclonal antiserum and anti-hEGF monoclonal antibody (MAb) were used for the study. Light microscopic immunohistochemistry with monoclonal and polyclonal antibodies showed that hEGF-like immunoreactivity was strongly positive in the myoepithelial cells and weakly positive in the secretory cells of eccrine sweat glands. In apocrine sweat glands, it was strongly positive in the secretory cells as well as in the myoepithelial cells. Immunoelectron microscopy with polyclonal antibody showed that hEGF-like immunoreactivity was present in secretory granules of apocrine secretory cells. These granules had mitochondrion-like internal structure. No reactivity was observed on the eccrine secretory cells by immunoelectron microscopy. Neither dark cell granules nor mitochondria in eccrine secretory cells were labeled with anti-hEGF antibody. In both eccrine and apocrine sweat glands, hEGF-like immunoreactivity was diffusely present in the cytoplasm of myoepithelial cells. However, nuclei and mitochondria of myoepithelial cells were devoid of immunoreactivity for hEGF. Our observations indicate that apocrine sweat glands may secrete more hEGF in the sweat than eccrine sweat glands.

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