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.

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