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Biomedical subjects

A G Messenger

Publications and source records attributed to A G Messenger.

At least 19 recordsLinked to original sources
PubMed1992

Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo.

Androgens are major regulators of human hair growth, but their effects vary: many follicles are stimulated by androgens, e.g., beard; some remain unaffected, e.g., eyelashes; whereas scalp follicles undergo regression and balding in genetically disposed individuals. Because the dermal papilla controls many aspects of the hair follicle, androgens may act via the dermal papilla, affecting the other follicular components indirectly. In this hypothesis androgens would alter dermal papilla cell production of regulatory substances, e.g., growth factors and/or extracellular matrix components. To test this theory the mechanism of androgen action has been compared in primary lines of dermal papilla cells cultured from androgen-dependent follicles and relatively androgen-independent non-balding scalp. Androgen receptor levels were assayed by saturation analysis (9-10 points; 0.05-10 nmol/l) using the synthetic androgen [3H]-mibolerone and specificity was confirmed by competition studies. Androgen metabolism was investigated both intracellularly and in the media after a 2-h incubation with 5 nM [3H]-testosterone. Carrier and [14C] steroids were added to the extracts before separation by thin-layer chromatography; steroid identity was confirmed by recrystallization. Dermal papilla cells from androgen-dependent follicles contained higher levels of specific, high-affinity, low-capacity androgen receptors than non-balding scalp cells. Testosterone metabolism also varied with beard, public and scalp cells containing testosterone and androstenedione intracellularly, but only beard cells producing 5 alpha-dihydrotestosterone, in line with the scanty beard growth found in 5 alpha-reductase deficiency. Elsewhere we have shown that cultured dermal papilla cells produce extracellular matrix components and mitogenic factors. These results all concur with our original hypothesis and suggest that further studies of such cells may elucidate the paradoxical effects of androgens on human hair follicles.

Androgens↗
PubMed1992

Glycosaminoglycan synthesis by cultured human hair follicle dermal papilla cells: comparison with non-follicular dermal fibroblasts.

The extracellular matrix of the hair follicle dermal papilla is rich in glycosaminoglycans, the expression of which varies during the hair growth cycle being maximal in anagen and becoming undetectable as the follicle enters telogen. These observations, together with other experimental and clinical evidence, suggest that glycosaminoglycans may be involved in regulating hair growth. To investigate the metabolism of glycosaminoglycans by the dermal papilla we have measured the incorporation of radiolabelled precursors into glycosaminoglycans released into extracellular matrix and culture medium by cultured human dermal papilla cells. We also studied glycosaminoglycan synthesis by cells cultured from the lower follicular connective tissue sheath and by non-follicular dermal fibroblasts. Compared with dermal fibroblasts, dermal papilla cells showed a three to fourfold higher level of incorporation of 35S-sulphate and 3H-glucosamine into extracellular matrix glycosaminoglycans. Dermal papilla cells also released more 3H-glucosamine-labelled glycosaminoglycan into culture medium than dermal fibroblasts but there was no difference in 35S-sulphate labelling. These findings indicate that dermal papilla cells maintain a high level of glycosaminoglycan synthesis in vitro. Specific enzyme/chemical degradation showed that dermal papilla cells and dermal fibroblasts synthesized the same glycosaminoglycan types. However, the results suggested that dermal papilla glycosaminoglycans are less sulphated than those synthesized by dermal fibroblasts and that a higher proportion of sulphated glycosaminoglycans is retained in an extracellular matrix. The synthesis of glycosaminoglycans by connective tissue sheath cells was similar to that of dermal papilla cells, supporting the view that the dermal papilla and connective tissue sheath share certain properties.

Cells, Cultured↗
PubMed1992

Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp.

Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age-related; androgen-potentiated changes also occur in the prostate. The mesenchyme-derived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0.05-10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control. Specific high-affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgen-insensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1991

Distribution of proteoglycans during the hair growth cycle in human skin.

The involvement of proteoglycans in hair growth has been recognized through the observation of increased hair growth in diseases such as the mucopolysaccharidoses and pre-tibial myxedema, which involve an increase in skin proteoglycan content. In an attempt to understand this, we have examined the distribution of chondroitin 6 sulphate (C6S), unsulphated chondroitin (COS), dermatan sulphate (DS), and heparan sulphate proteoglycans (HSPG) in frozen tissue sections of normal scalp by immunostaining. Results show that during anagen, the thick connective tissue sheath around the follicle strains strongly for C6S, COS, and DS. COS is uniquely associated with this region and is not found beneath the epidermis or infundibular epithelium. HSPG is, however, localized in the basement membrane zone adjacent to the outer root sheath. In addition, all of these proteoglycans are localized in the dermal papilla. In mid-catagen, we observed significant loss of C6S and COS staining from both the dermal papilla and the connective tissue sheath, but no decrease in staining for HSPG. In late catagen, very little staining of C6S and COS was observed. In early anagen, we observed that C6S was again present in the connective tissue sheath and dermal papilla; however, COS staining appeared to be weaker and less closely associated with the follicle. HSPG staining was observed in early anagen in a pattern very similar to that found for other basement membrane components. Results for DS were not obtained for catagen or early anagen. These results provide further evidence that hair growth is associated with the presence of chondroitin proteoglycans in the follicle environment and that the cessation of growth is associated with their removal. Further studies are underway to characterize the relationship between hair growth and proteoglycans.

Adult↗
PubMed1991

Effect of androgens on the growth of cultured human dermal papilla cells derived from beard and scalp hair follicles.

Androgens stimulate hair growth in some areas, e.g., beard, but may cause regression and baldness on the scalp. The mesenchyme-derived dermal papilla is believed to regulate many aspects of hair growth. It is probable that androgens exert their effect on hair growth via the dermal papilla. In this study the effect of androgens on the growth of cultured dermal papilla cells from beard and non-balding scalp was assessed. Dermal papilla cells from beard hair follicles and non-balding scalp were cultured in vitro in the presence and absence of different concentrations of testosterone or the synthetic, non-metabolizable androgen, mibolerone. Cell growth was reflected by the incorporation of 3H-thymidine. The presence of either androgen did not significantly alter DNA synthesis at any of the concentrations examined in either type of cell line. These results do not mean that dermal papilla cells do not respond to androgens in vitro, but that the measurement of cell growth is an inappropriate method of assessment. Androgens may well stimulate the synthesis of specific proteins that could influence the hair follicle.

Androgens↗
PubMed1991

Expression of basement membrane proteins and interstitial collagens in dermal papillae of human hair follicles.

The expression of basement membrane molecules and interstitial collagens in human hair follicle mesenchyme was studied by immunohistochemical staining of tissue sections and of cells cultured from dermal papillae. Type I and type III collagens were found in the dermal sheath and in the dermal papilla throughout the hair cycle. Laminin and type IV collagen were expressed at the outer root sheath basement membrane and in the extracellular matrix of the dermal papilla of anagen and catagen follicles. In telogen follicles, where the volume of the dermal papilla extracellular matrix is much reduced, outline staining of dermal papilla cells for laminin and type IV collagen was still apparent. Staining for bullous pemphigoid antigen was also seen at the outer root sheath basement membrane extending to the lower tip of the hair bulb. In anagen follicles, there was no staining for bullous pemphigoid antigen at the interface between hair bulb epithelium and the dermal papilla and no staining within the dermal papilla. However, linear staining for bullous pemphigoid antigen became continuous around hair follicle epithelium during catagen and telogen. Cells cultured from human dermal papillae also stained for interstitial collagens, type IV collagen and laminin. However, similar results were obtained when cultured dermal fibroblasts were stained with the same antibodies. The expression of basement membrane proteins in human dermal papillae resembles that seen in follicles from other mammalian species and suggests that this is relevant to dermal papilla function. Cultured dermal papilla cells express a similar pattern of interstitial collagens and basement membrane proteins to those seen in tissue sections but this finding is not specific to dermal papilla cells.

Antibodies, Monoclonal↗
PubMed1990

Expression of extracellular matrix in hair follicle mesenchyme in alopecia areata.

Human hair follicle mesenchyme contains a distinctive extracellular matrix which varies in volume and composition in concert with the hair growth cycle. To investigate the possibility that mesenchymal function is disturbed in alopecia areata we have studied the expression of extracellular matrix constituents in scalp biopsies from 14 patients by immunohistochemical staining for basement membrane proteins, proteoglycans and interstitial collagens. The staining patterns in follicles from non-lesional scalp were normal. Miniature anagen follicles from bald patches also showed relatively normal expression of basement membrane proteins and proteoglycans. However, in some large anagen follicles from lesional sites, there was loss of the normal staining pattern for chondroitin-6-sulphate in the dermal papilla. In lesional catagen follicles, the glassy membranes showed marked convolution and thickening. These structures stained strongly for laminin and type IV collagen but only weakly for interstitial collagens.

Adolescent↗
PubMed1990

Dysplastic naevi in association with partial deletion of chromosome 11.

A patient is reported who developed dysplastic naevi at an early age. He also suffered from a syndrome including Wilms' tumour, aniridia, mental retardation and diabetes mellitus in association with an interstitial deletion of the short arm of chromosome 11. It is suggested that genetic factors may be important in sporadic as well as familial cases of the dysplastic naevus syndrome.

Adult↗
PubMed1990

Scarring alopecia in psoriasis.

Scalp biopsies were taken from 3 patients with a scarring alopecia associated with severe scalp psoriasis. The histological findings in each case showed inflammatory destruction of the infundibular region of the hair follicle. The similarity of these changes in each case strongly suggests an association with the psoriasis.

Adult↗
PubMed1989

Sunbed-induced pseudoporphyria.

The clinical details of four fair-skinned women with recurrent blistering and skin fragility are presented. All had considerable sun-exposure and had used sunbeds for years. Specific causes of bullous dermatoses including drug ingestion, porphyria, cutaneous amyloidosis and epidermolysis bullosa acquisita were excluded. Long-term recurrent exposure to high doses of sunbed radiation in chronically sun-damaged skin appears to be a further cause of pseudoporphyria.

Adult↗