ISSN:1660-5527    

DOI:10.1159/000211263

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000211264

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The human hair follicle cycles in active growth and resting phases controlled by a complex network of biochemical processes, yet to be fully understood. It is well known that hair follicles on scalp respond to androgens by a shortening of the anagen growth phase causing hairs to regress to a finer, thinner texture. The target tissue androgens, testosterone, and dihy-drotestosterone can circulate systemically to skin or can be formed locally in hair follicles and sebaceous glands by specific enzymes in the steroid cascade. Kinetic constants have been evaluated for several enzymes which mediate dihydrotes-tosterone formation, including 5a-reductase, and the cyto-chrome P-450 aromatase enzyme in isolated human hair follicles and sebaceous glands from scalp of men and women with androgenetic alopecia. The levels of these enzymes differed between men and women, and from frontal versus occipital sites within the same patient, indicating that similar steroid mechanisms may be taking place in men and women, but the amount or level of enzymes vary, perhaps explaining why men have more severe patterns of hair loss than women. Knowing the differences between men and women with androgenetic alopecia could shape more effective treatment options in the future.

ISSN:1660-5527    

DOI:10.1159/000211265

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The slow-cycling cells in the bulge of the outer root sheath may represent stem cells for the hair follicle. With each new anagen (growing) phase bulge cells would give rise to a population of transient-amplifying cells which differentiate into outer root sheath and matrix keratinocytes. The lowermost part of the telogen (resting) follicle is composed of bulge cells lying in close proximity to the dermal papilla. In the mouse the first hair follicle growth is characterized by rapid follicular neogen-esis, but the second and third growth cycles follow the normal follicular growth pattern. We have examined activity of cells in the bulge at the onset of anagen (growing phase) in the third hair cycle in Sencar mice, by treating animals at the end of the second telogen with colchicine to localize mitotic activity in the hair follicle. Mitoses were only seen in bulge cells during early anagen. This confirms that they proliferate transiently, solely at the onset of anagen and strongly supports the suggestion that bulge cells are the origin of the whole lower follicle in anagen.

ISSN:1660-5527    

DOI:10.1159/000211266

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

When plucked follicles were cultured together with isolated dermal papillae in a collagen gel matrix, outer root sheath cells (ORSCs) grew more rapidly and actively than without the papillae. Cultured dermal papilla cells also activated the colony growth of ORSCs in vitro. These results may suggest the existence of some papilla-derived factor(s) activating the growth of ORSCs. In cultures of excised whole follicles whose dermal papilla had been removed, epithelial cells of bulb matrix origin grew out from the bulbous portion, and formed spikes. When a dermal papilla was implanted close to the follicle, the spikes elongated toward the papilla, and finally reached and surrounded it. This finding suggests that dermal papillae may produce some factor(s) attracting epithelial cells of hair bulb origin. In cultures of excised whole follicles, when the dermal papilla remained originally positioned in contact with the hair bulb matrix, the hair and follicle elongated for more than 1 week. But when the dermal papilla was detached from the bulb matrix, the matrix cells proliferated into the gel and formed a hair-follicle-like structure (folliculoid). In cultures of excised whole follicles whose papilla-matrix junction had been damaged by dispase, elongation of the hair and follicle was almost completely suppressed. Thus, the attachment of the dermal papilla to the bulb matrix appears to be necessary for normal hair and follicle growth.

ISSN:1660-5527    

DOI:10.1159/000211267

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

All four of the principle dermal and epidermal cell types from the adult hair follicle (dermal papilla and sheath, germinative epidermal and outer root sheath) can now be grown in culture. The germinative epidermal cells from the source of the hair fibre appear to be the most visually distinctive of these populations, but all four can be morphologically, synthetically and behaviourally distinguished from general interfollicular skin cells. The germinative population also most obviously exhibit many classical stem cell attributes, but the interactive and inductive capabilities of all of the cell types, in addition to their multipotential natures, highlights that they all share an intriguing level of developmental flexibility.

ISSN:1660-5527    

DOI:10.1159/000211268

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Androgens are major regulators of human hair growth with paradoxically different effects on hair follicles depending on their body site. They stimulate terminal growth in many regions including the face, have no effect on eyelashes, but may cause inhibition and balding on the scalp in genetically disposed individuals. How this occurs is unknown. However, androgens may act on the hair follicle via the cells of the dermal papilla; these would then influence the other cells of the hair follicle by altering the production of regulatory substances such as growth factors and/or extracellular matrix components. Therefore, primary lines of dermal papilla cells have been established from androgen-sensitive hair follicles, such as beard, and control, relatively androgen-independent, non-balding scalp cells and their mechanism of androgen action has been compared. Isolated beard dermal papillae were larger than those from scalp follicles. Although dermal papilla cells did not respond to in vitro androgens by alterations in growth, androgen-dependent dermal papilla cells contained higher levels of specific, low capacity, high affinity androgen receptors than non-balding scalp cells. The ability of the cells to metabolise testosterone to 5α-dihydrotestosterone in culture also varied in parallel to that predicted from studies of hair growth in the 5α-reductase deficiency syndrome. These results support the hypothesis that androgens act via the dermal papilla. They also show that dermal papilla cells retain differences in gene expression in culture which appear to correspond with their androgenic response in vivo. Further studies of such cells should help elucidate why bald men can grow beard

ISSN:1660-5527    

DOI:10.1159/000211269

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Biological and biochemical mechanisms of hair growth are difficult to study in vivo; therefore the development of in vitro models is of great interest. Today, we have of our disposal reliable techniques to cultivate cell populations and entire components of terminal hair follicles; however, in vitro culture models for cells derived from vellus hair follicles have not yet been established. In this study, we present a technique for cultivating vellus hair follicle-derived keratinocytes (VHK) and we present first findings on their characterization. Primary cultures of VHK were obtained as outgrowths of cultured intact vellus hair follicles prepared by microsurgical means after incubation of full-thickness human skin with dispase. (1) VHK cultures reached confluency after 16–20 days and 3–4 subcultures were possible. (2) VHK were characterized as epithelial cells by light and electron microscopy. (3) A multi-layered stratified epithelium with 8–10 cell layers was observed by electron microscopy presenting abundant keratinos-omes in individual cells in contrast to outer root sheath keratinocytes. (4) Synthesis studies of two glycoproteins characteristic for undifferentiated (gp 38) and for differentiated (gp 80) keratinocytes revealed higher synthesis levels for gp 80 and lower levels for gp 38 in VHK as compared to normal epidermal keratinocytes in vitro. These findings suggest a distinct morphologic and differentiation pattern of VHK in culture. This experimental model provides a new tool to study mechanisms of hair growth regulation in vellus hair follicles and to compare them to those of terminal hair foll

ISSN:1660-5527    

DOI:10.1159/000211270

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To investigate the varying response of the pilosebaceous unit to androgens functional studies were performed on the effects of testosterone and 5α-dihydrotestosterone on cultured human sebocytes derived from different skin regions. In addition, the effect of spironolactone on the proliferation of androgen-stimulated human sebocytes derived from facial skin was evaluated. Testosterone (1O-11 to 10-5M), 5α-dihydrotestosterone (10-11 to 10-5M) and spironolactone (10-12 to 10-7M) were added for 10 days as single substances or in combinations to human sebocytes in secondary culture maintained in a serum-free medium. Cell proliferation was assessed using a fluorometric assay. Intracellular lipids were extracted from sebocytes treated with androgens (10-7M) for 10 days after con-fluency. Testosterone inhibited the proliferation of sebocytes derived from the legs with a 50%-inhibitory concentration at 10-5M and induced a 50% decrease of intracellular lipids. In contrast, 5 α-dihydro testosterone stimulated the activity of leg sebocytes with a 50% increase of proliferation at 10-5M, and a 175% increase of intracellular lipids. On the other hand, the proliferation of facial sebocytes was significantly stimulated by testosterone with a 50%-stimulatory concentration at 10-6 to 10-5Mand mostly by 5α-dihydrotestosterone with a 50% enhancement at 10-8 to 10-7M. Spironolactone inhibited the proliferation of facial sebocytes in a dose-dependent manner with a 25%-inhibitory concentration at 10-9M. Simultaneous treatment of facial sebocytes with spironolactone and testosterone or 5α-dihydrotestosterone resulted in decreased proliferation when compared to the growth obtained under androgens alone. Moreover, spironolactone at 10-7M neutralized the stimulatory activity of 5α-dihydrotestos-terone at all concentrations tested. In contrast to previous reports of no androgen effect on human dermal papilla cells in culture, our results show a specialized response of human sebocytes to androgens dependent on the localization of the sebaceous glands. The direct inhibition of sebocyte proliferation by spironolactone and its antagonistic activity to androgens at the cellular level are indicative of a receptor-monitored e

ISSN:1660-5527    

DOI:10.1159/000211271

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

On maintenance in supplemented Williams E medium, human hair follicles grow at the normal rate, and retain their normal anagen morphology, for up to 10 days. This permits us to study their metabolism under near-physiological conditions. The ATP content of freshly isolated follicles was 124.4 ± 10.6 pmol/follicle (mean ± SEM; n = 50). The energy charge was 0.81 ± 0.08 and the glycogen content 2.3 ± 0.3 nmol/follicle. These did not alter significantly during any metabolic studies, which were performed for up to 6 h in supplemented Williams E medium. We found that the major fuel was glucose, which at physiological concentrations yields 5.47 ± 0.77 nmol ATP/follicle/h, but 90% of the glucose was metabolised to lactate, and only 10% oxidised. Glutamine was also an important fuel, generating 2.16 ± 0.33 nmol ATP/follicle/h, but this too was largely metabolised to lactate rather than oxidised. Lipid fuels such as palmitate or β-hydroxybutyrate only yielded 0.72 ± 0.15 and 0.72 ± 0.14 nmol ATP/follicle/h, respectively, and their oxidation did not inhibit glucose utilisation. No glucose-fatty acid cycle operates in the hair follicle, therefore, but a glucose-glutamine cycle does, since the presence of glutamine will inhibit glucose uti

ISSN:1660-5527    

DOI:10.1159/000211272

出版商:S. Karger AG    

年代:1994

数据来源: Karger