Dermoscopic characteristics, such as black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs, are useful clinical indicators for AA.

Androgen receptor (AR) is a hormone-activated transcriptional factor that can bind to androgen response elements and that regulates the transcription of target genes via a mechanism that presumably involves cofactors. We report here the cloning of a novel AR coactivator ARA55 using a yeast two-hybrid system. ARA55 consists of 444 amino acids with the predicted molecular mass of 55 kDa and its sequence shows very high homology to mouse hic5, a TGF-␤1-inducible gene. Yeast and mammalian two-hybrid systems and co-immunoprecipitation assays all prove ARA55 can bind to AR in a liganddependent manner. Transient transfection assay in prostate cancer DU145 cells further demonstrates that ARA55 can enhance AR transcriptional activity in the presence of 1 nM dihydrotestosterone or its antagonists such as 100 nM 17␤-estradiol or 1 M hydroxyflutamide. Our data also suggest the C-terminal half of ARA55, which includes three LIM motifs, is sufficient to interact with AR. Northern blot and polymerase chain reaction quantitation showed ARA55 can be expressed differently in normal prostate and prostate tumor cells. Together, our data suggests that ARA55 may play very important roles in the progression of prostate cancer by the modulation of AR transactivation. The androgen receptor (AR)1 is a member of the steroid receptor (SR) superfamily and plays an important role in male sexual differentiation and prostate cell proliferation (1). The well conserved DNA binding domain (DBD) within AR has two zinc finger structures that are involved in DNA binding. The C-terminal region of the AR, including the hinge region and the ligand-binding domain, is responsible for the functions of dimerization and androgen binding. The N-terminal region is involved in the transcriptional activation of AR.The discovery of transcriptional interference/squelching of SRs provided the concept of the existence of transcriptional cofactors that mediate SR function (2, 3). Recently, several putative cofactors (either coactivators or corepressers) for SRs have been identified and characterized (4,5). Further studies of the interaction of SRs with these cofactors suggested that these SR-cofactor complexes play essential roles for the regulation of SRs target gene transcription by interaction with general transcription factors and the remodeling of chromatin (4, 5).The in vivo significance of these cofactors and their relationship to diseases, however, remains unclear. Recently, an estrogen receptor coactivator, AIB1, was identified with higher expression in ovarian cancer cell lines and breast cancer cells than in other cell lines tested (6), implying that increased expression of cofactors might be involved in some hormoneresponsive tumors. The question whether cofactors of AR, the major promoter of prostate tumor growth, can also play vital roles for the maintenance of androgen-dependent status is thus of vital interest.Here we report for the isolation and characterization of a novel AR coactivator, ARA55, which can bind to wild type AR (wtAR) and mutant AR (m...

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8+ T cells, CD4+ T cells and NKGD2+ NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

The gene encoding a transmembrane glycoprotein LIG-1, of which the extracellular region was organized with the leucine-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease 'psoriasis'. LIG-1 was expressed in basal cells of the epidermis and outer root sheath cells of hair follicles in mice. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 inversely correlates with proliferative ability of epidermal keratinocytes. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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Androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as 'androgen paradox'. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5a-reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF-1 as positive mediators from beard DP cells and of TGF-b1, TGF-b2, dickkopf1 and IL-6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation of hair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/b-catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA.Key words: 5a-reductase -androgen -androgen receptor -growth factor -Wnt Accepted for publication 31 August 2012 ScopeHair growth and cycling are regulated by many hormones (1), and the effect of androgens, in particular, has been well known for a long time. However, many questions about androgen metabolism and function in hair follicles remain unanswered. In this review, we have examined published evidence and reconsidered the perspective on molecular physiology and pathophysiology of the effect of androgens on hair growth. Clinical view of androgens and hair growthAndrogens regulate human hair growth, and their effects vary depending on body sites. Before puberty, there is only vellus hair in the pubic and axillary areas of males and females, but when androgens increase in puberty, vellus hair follicles develop into terminal ones, producing larger, curlier and darker hair shafts. In males, androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA) and this reciprocal effect is known as the 'androgen paradox' (2,3). Historically, the first scientific description of the effect of androgens on AGA was published by James B Hamilton in 1942 (4) based on his clinical observation of androgen induction of AGA in the males with testicular insufficiency. On the other hand, Margaret Chieffi was the first to scientifically prove the positive action of androgen on beard growth in males in clinical experiments to investigate the effect of testosterone injection on beard growth of elderly males (5). In male pseudohermaphrodites, with 5aR2 deficiency, normal axillary and female-pattern pubic hair growth but no or little beard growth and no AGA is seen (6-9), indicating that 5aR2 is necessary for beard growth and AGA development but not for pubic and axillary hair growth. In female hirsutism patients, androgenic factors, including polycystic ovary syndrome, are responsible for up to 80% of the condition (10), suggesting that androgens can regulate hair growth in not only males but also in females, so t...

In recent years, the usefulness of trichoscopy (scalp dermoscopy) has been reported for hair loss diseases. Here, characteristic trichoscopic features of common hair loss diseases are described using a DermLite II pro or Epilight eight. Characteristic trichoscopic features of alopecia areata are black dots, tapering hairs (exclamation mark hairs), broken hairs, yellow dots and short vellus hairs. In androgenetic alopecia (AGA), hair diameter diversity (HDD), perifollicular pigmentation/peripilar sign and yellow dots are trichoscopically observed. In all cases of AGA and female AGA, HDD more than 20%, which corresponds to vellus transformation, can be seen. In cicatricial alopecia (CA), the loss of orifices, a hallmark of CA, and the associated changes including perifollicular erythema or scale and hair tufting were observed. Finally, an algorithmic method for trichoscopic diagnosing is proposed.