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Background Glial cell line–derived neurotrophic factor (GDNF) and a related family member, neurturin (NTN), and their cognate receptors (GFRα-1 and GFRα-2, for GDNF and NTN, respectively) are distal members of the transforming growth factor-β superfamily. They are involved in the control of murine hair follicle (HF) cycling. This study tests the hypothesis that GDNF and NTN, and their cognate receptors, are expressed in the human HF and their expression varies in the different stages of the HF cycle. Methods The expression pattern of these proteins was examined in human HF by immunofluorescence, immunoalkalinephosphatase staining methods, and reverse transcription-polymerase chain reaction (GDNF). The functional effects (GDNF and NTN) were examined in organ culture of the microdissected HFs. Results GDNF, NTN, GFRα-1, GFRα-2, and c-Ret proteins were weakly expressed in catagen and telogen HFs. In contrast, they were strongly expressed in the epithelial and mesenchymal compartments of the anagen HF. GDNF gene was transcribed, both in the human scalp skin and in the isolated anagen HFs (reverse transcription-polymerase chain reaction). In HF organ culture, GDNF (but not NTN) increased the number of the proliferating HF keratinocytes (Ki 67 + cells). GDNF partially protected HFs from transforming growth factor-β2–induced premature catagen transition. Limitations None. Conclusions GDNF, NTN, GFRα-1, GFRα-2, and c-Ret proteins are differentially expressed in the different stages of HF cycle. GFRα-mediated signaling involves c-Ret and may play a role in human HF biology.

Background Heat shock protein (HSP) is a molecular chaperone involved in protein folding, assembly, and transport and in the regulation of cell growth and differentiation. HSP27 protein is expressed in murine hair follicle (HF) and in human skin during fetal development. In this investigation we hypothesized that HSP27 protein is expressed in the human scalp skin and its expression in HF changes with the transitions form anagen → catagen → telogen stages. Methods To test this hypothesis, the immunoreactivity of HSP27 protein was examined in human scalp skin by immunofluorescent method. A total of 50 normal human scalp skin biopsy specimens were examined (healthy women, age 53-57 years). In each case, 50 HF were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Results HSP27 protein expression was prominent in human scalp anagen, and weak in both catagen and telogen HFs. Within HF, HSP27 protein immunoreactivity was prominent in the outer root sheath, inner root sheath, precorteocytes, and corteocytes of the hair shaft. In addition, HSP27 protein expression was prominent in the epidermis, sebaceous glands, sweat glands, and arrector pili muscles. Limitations Only some types of heat shock proteins are known to date. Also, our knowledge about the exact molecular mechanisms involved in the interactions among these protein and other molecular chaperones is still incomplete. Conclusions Our investigation reports, for the first time, the expression patterns of HSP27 in human scalp skin and HF. The differential expression of HSP27 during HF cycling suggests its possible roles in human HF biology.

Background The p75 neurotrophin receptor (p75NTR) is a death factor (apoptosis-promoting protein) that belongs to the tumor necrosis factor receptor superfamily of membrane proteins. In the murine hair follicle (HF) model, p75NTR plays a critical role during HF morphogenesis, functioning as a receptor that negatively controls HF development. p75NTR signaling is involved in the control of keratinocyte apoptosis during catagen. To date, knowledge about the expression pattern of p75NTR protein in human scalp skin and HFs is limited. In this investigation we hypothesized that p75NTR protein is expressed in human scalp skin and its expression in HFs fluctuates with the transitions from anagen → catagen → telogen stages. Methods To test this hypothesis, the immunoreactivity of p75NTR protein was examined in human scalp skin by immunofluorescent and immunoalkaline phosphatase methods. A total of 50 normal-appearing human scalp skin biopsy specimens were examined (healthy women age 53-57 years). In each case, 50 HFs were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Results We found variations in p75NTR protein expression with HF cycling. p75NTR expression was negligible in early, mid, and mature anagen and weak during late anagen. p75NTR expression was moderate during anagen-catagen transition. It was strong in both catagen and telogen HF. Also, p75NTR protein expression was strong in the stratum corneum (epidermis), dermal fibroblasts, blood vessels, nerve endings, adipocytes, and both sebaceous and sweat glands. Limitations Our knowledge about other proteins (prosurvival and pro-apoptotic molecules) interacting with p75 is incomplete. Conclusions Our investigation reports, for the first time, the expression patterns of p75NTR in human scalp skin and HFs. p75NTR protein expression exhibited significant hair cycle-dependent fluctuation, suggesting a possible role in human HF biology.