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K S Stenn

Publications and source records attributed to K S Stenn.

At least 19 recordsLinked to original sources
PubMed1999

Androgen-induced delay of hair growth in the golden Syrian hamster.

The golden Syrian hamster flank organ has been used to study the stimulatory effect of androgens on sebaceous glands and hair. Androgens cause the sebaceous glands and hair follicles in this organ to grow. We have made the novel observation that exogenously administered androgen, testosterone propionate (TP), suppresses hair growth in the area surrounding the flank organ. When given in a time-release (systemic) subcutaneous dosage form (pellet), 25 mg TP inhibited the regrowth of clipped hair in peri-flank organ skin for up to 21 days; however, by 28 days hair grew back to the same extent as in controls. The peak serum level of testosterone in TP-treated animals occurred at 14 days, and declined thereafter. When two separate TP pellets (25 mg/pellet) were administered 14 days apart in order to maintain high serum levels for 28 days, the amount of hair regrowth after 35 days was identical to animals receiving a single TP pellet or placebo. This suggests that the systemic level of testosterone was not the only factor in hair regulation. Hair growing within the flank organ appeared to be unaffected by TP administration. In the golden Syrian hamster, androgen, as in humans, can exert stimulatory and inhibitory effects on hair growth depending on the body site. We conclude that this animal model could serve as a useful system to investigate the mechanisms responsible for the opposing effects of androgen on hair growth.

Analysis of Variance↗
PubMed1999

What controls hair follicle cycling?

Despite more than a hundred years of professional hair research, and substantial recent progress in unravelling the molecular controls of hair follicle morphogenesis, the chronobiological control system that cyclically drives the hair follicle through dramatic remodelling processes between phases of growth (anagen), regression (catagen), and relative resting (telogen) have remained disappointingly obscure. In view of the vast literature that has become available over the past decades on numerous genetic, biochemical, cellular and pharmacological aspects of hair growth follicle control under physiological and pathological conditions, it is astounding how comparatively few researchers in the field have published theoretical concepts that explore how hair follicle cycling might be controlled. Since this question is at the very heart of basic and clinically applied hair biology, it deserves a much more systematic and serious public exploration, which the following contributions are designed to stimulate.

Animals↗
PubMed1998

Differential subtraction display: a unified approach for isolation of cDNAs from differentially expressed genes.

We have developed a novel efficient approach, termed differential subtraction display, for the identification of differentially expressed genes. Several critical parameters for the reproducibility and enhanced sensitivity of display, as well as steps to reduce the number of false positive cDNA species, have been defined. These include- (a) use of standardized oligo(dT)-primed cDNA pools rather than total RNA as the starting material for differential display, (b) critical role of optimal cDNA input for each distinct class of primers, (c) phenomena of primer dominance and interference, and (d) design of a novel set of enhanced specificity anchor primers. Introduction of an efficient subtractive hybridization step prior to cloning of cDNA species enriches the bona fide cDNA species that are either exclusively present in one sample (+/-) or show altered expression (up-/down-regulation) in RNA samples from two different tissues or cell types. This approach, in comparison to differential display, has several advantages in terms of reproducibility and enhanced sensitivity of display coupled to the cloning of enriched bona fide cDNA species corresponding to differentially expressed RNAs.

Animals↗
PubMed1997

Expression of two Ig family adhesion molecules in the murine hair cycle: DCC in the bulge epithelia and NCAM in the follicular papilla.

The hair cycle involves remodeling of cells and of cell groups into a complex follicular structure. During skin appendage development, adhesion molecules such as neural cell adhesion molecule (NCAM) and deleted in colon carcinoma (DC) participate in the formation of cell groups. NCAM has been found to be expressed in the mesenchyme during mouse hair follicle induction. DCC expression has been observed in the epithelial cells of the developing feather. We postulate that these two molecules may also define cell groups in the cycling hair follicle. Here we report their spatio-temporal expression patterns during the depilation-induced murine hair cycle. NCAM expression was also examined in positive and negative hair-inductive follicular papilla cell lines. Throughout the hair cycle, DCC expression was confined to the basal keratinocytes of the epidermis and the epithelial portion of the hair follicle. During mid-anagen, two types of deleted in colon carcinoma staining were observed. One was a cell surface pattern seen in the epithelial cells in the bulge region where the follicular stem cells reside. The other was a diffuse cytoplasmic staining pattern in the transient hair follicle epithelia located below the bulge region. Prominent NCAM staining was observed in the follicular papilla throughout the hair cycle and was accompanied by weak staining of the matrix epithelia. NCAM expression correlated with hair induction by a follicular papilla cell line. The results suggest that DCC and NCAM define the permanent cell groups of the hair follicle and that NCAM is important for hair induction.

Animals↗
PubMed1997

Fibroblast-dependent induction of a murine skin lesion similar to human nevus sebaceus of Jadassohn.

Using a nude mouse grafting model, we have demonstrated that normal-haired skin is regenerated in a graft containing hair buds and dissociated dermis. Altering the dermal component leads to changes typical of the human nevus sebaceus of Jadassohn (NSJ). The murine lesion is characterized by sebaceous gland hyperplasia, abortive hair follicles, and epidermal hyperplasia. The development of the NSJ-like lesion is independent of the epidermal component but dependent on a specific dermal fibroblast combination, namely, a hair-inductive follicular papilla fibroblast cell line plus BALB/c 3T3 fibroblasts. Non-hair-inductive follicular papilla cell lines in combination with BALB/c 3T3 fibroblasts are unable to induce the NSJ-like structure, indicating that hair-inductive signals play a central role in its pathogenesis. BALB/c 3T3 fibroblasts in combination with total cells from dissociated neonatal dermis produce abortive hair follicles, but the sebaceous gland hyperplasia is suppressed, suggesting the presence of suppressive endogenous dermal factors. The data suggest that (a) pilosebaceous induction is a multistep process and (b) the pathogenesis of NSJ involves perturbation of a complex array of inductive mesenchymal (dermal) signals. This paper describes the first animal model of NSJ and provides evidence that development of the human lesion could depend entirely on aberrant dermal cells.

3T3 Cells↗
PubMed1996

Hair follicle growth controls.

Research in hair biology has embarked in the pursuit for molecules that control hair growth. Many molecules already have been associated with the controls of hair patterning, hair maturation, and hair cycling and differentiation. Knowing how these molecules work gives us the tools for understanding and treating patients with hair disorders.

Adult↗
PubMed1996

Fibroblast-dependent induction of a murine skin lesion with similarity to human common blue nevus.

In an attempt to define epithelial-mesenchymal interactions in skin appendage formation, we have been studying a nude mouse grafting model that permits the combination of heterotypic and heterochronic epithelial and mesenchymal cells. In this study using neonatal hair bud cells combined with various mesenchymal cell preparations, we show that one can regenerate near-complete skin with intact epidermal and dermal layers plus mature hair follicles. It was determined that the character of the resulting regenerated skin could be manipulated as a function of the specific mesenchymal component. Lack of dermal cells resulted in a scar, whereas inclusion of a suspension of dissociated total dermal cells resulted in near-complete skin regeneration, and in the presence of follicular papilla fibroblasts (both hair-inductive and non-hair-inductive) or NIH3T3 fibroblasts, the reconstitution had similarity to the common blue nevus. The results indicate that 1) a stimulant of human common blue nevus can be produced in an animal model, 2) the underlying disorder of the lesion in mice appears to be entirely dermal in origin, arising independent of the epidermal component, and 3) complex dermal cell interactions involving lesion-initiative and lesion-suppressive activities underlie the pathogenesis. This experimental system will serve as a valuable tool in elucidating cutaneous dermal-epidermal signals in normal skin as well as the alteration of these signals in malformations such as the hamartoma described here.

3T3 Cells↗
PubMed1995

Changes in expression of apoptosis-associated genes in skin mark early catagen.

Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcriptase-polymerase chain reaction, we examined in this study the expression in total skin, throughout one hair cycle, of a series of regulatory genes associated with apoptosis. We show that gene expression within skin is hair-cycle-dependent. Transforming growth factor-beta was expressed immediately before catagen; therefore, it might be involved in the early signaling of this process. Tumor necrosis factor-beta was expressed during catagen and might be involved in follicular apoptosis. Several proto-oncogenes and transcription factors have been described in the regulation of apoptosis in other systems. Here we show that the transcript levels of c-myc, c-myb, and c-jun changed immediately before or during early catagen and thus could be involved in the signaling or regulation of catagen. Levels of p53 remained constant throughout anagen and catagen, suggesting that p53 is not involved in the developmentally induced apoptosis of the hair follicle. The variable expression throughout the hair cycle of the genes described demonstrates the dynamic changes of the skin and underscores the importance of studying the complete hair cycle when characterizing any molecule in skin.

Animals↗
PubMed1994

Transection level dictates the pattern of hair follicle sheath growth in vitro.

Using a newly developed in vitro sheep hair culture system, we found that the pattern of sheath growth is a function of the level at which the follicle is transected. Two patterns are observed. The type 1 pattern, which occurs after the follicle is transected below the sebaceous gland, shows an equal elongation of the sheath and shaft. The type 2 pattern, which occurs when the follicle is cultured either after transection above the sebaceous gland or with an intact attached epidermis, is characterized by growth of hair shaft clean of sheath. These growth patterns, dictated by the transection level, are observed in both sheep and human follicles, are not dependent on the presence of the sebaceous gland itself, and are not influenced by the presence of co-cultured epidermis or infundibulum. Thymidine autoradiography demonstrates that transecting follicles beneath the sebaceous gland leads to an increase in DNA synthesis of the cells in the external root sheath, but does not alter DNA synthesis of the cells in the follicle matrix. Besides the obvious implications to wound closure, these findings indicate that the sebaceous gland demarcates a significant region of the follicle which influences sheath-shaft interactions and that the sheath and the shaft constitute coordinated cell populations which nevertheless respond distinctly to proliferative signals.

Animals↗
PubMed1994

Molecules of the cycling hair follicle--a tabulated review.

In this review we tabulated molecules which have been experimentally identified to be associated with, or play a role in, hair follicle growth. While compiling these data we were impressed by the fact that this field is only now beginning to be developed in terms of molecular analysis. Ironically, hair was used in some of the earliest molecular approaches to biologic structure (e.g. Astbury and Street, 1931), but the field did not develop from there. From our review we have come to the following conclusions. (1) As indicated by the growing number of reports dealing with follicle-associated molecules in the past 3 years, the field of hair biology has entered a new molecular era. (2) In many reported hair biology studies not enough emphasis has been placed on the fact that the follicle is a dynamic structure. All too often a study is limited to follicles of one particular phase of the cycle or one phase of development. Students in the field have to be more sensitive to the remarkable changes that this deceptively simple structure can undergo during its cycle. (3) Although we have not been able to find any molecules unique to the follicle, some of the structural molecules come close to an ideal tool. It is our impression that even more specific molecule tags will be found. Whether this requires a subtraction library approach or gene mapping of specific mutants is not yet clear. It would appear that the large, diverse family of intermediate filament-associated proteins will prove to be an excellent source of unique follicle-labeling molecules. (4) There is an acute need for molecules which distinguish the phases of the cycle, e.g. telogen from early anagen. Telogen is by far the most difficult phase to identify morphologically since the earliest phase of anagen and the latest phase of catagen may appear structurally like telogen. That these phases are functionally distinguishable must imply a molecular difference. As the number of recognized hair follicle-associated molecules and their interactions increase, it will be essential to assemble libraries of highly specific RNA and antibody probes for localization and mapping studies. We recognize that this review, as written, is imperfect. It is particularly deficient in making any effort towards identifying unifying principles of structure and function. We look forward to returning to this subject within 3 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Expression of the bcl-2 protooncogene in the cycling adult mouse hair follicle.

The hair follicle undergoes a cycle of growing, regressing, and resting phases (anagen, catagen, telogen, respectively). As the follicle enters catagen, the cells of the lower, cycling portion undergo a process of controlled cell death (apoptosis). Understanding the mechanism of apoptosis in the follicle should give insight into one of the control steps of hair cycling. In this study we sought the expression of bcl-2, a protooncogene associated with apoptosis control, in the cycling follicle of the adult mouse. Using a monoclonal antibody to the mouse protein we immunolocalized bcl-2 gene product in the cycling pelage follicle of the C57/B6 adult mouse. The protein was expressed in the follicular papilla (a non-cycling portion of the follicle) throughout the cycle-including telogen. The cycling follicular epithelium, however, showed positive antibody staining in anagen, which decreased in catagen and disappeared in telogen. In anagen the cells of the bulb, bulge, and basal layer of the outer root sheath expressed the bcl-2 protein. Understanding the action of this apoptosis-inhibiting molecule should serve to elucidate the dynamics of follicular cycling.

Animals↗