Hair Growth Cycle Research Articles

Einfluss von Melatonin auf die Physiologie des Haares

Melatonin, the pineal gland hormone and a strong antioxidant, has long been known, particularly in animal-experiment based research and the wool-producing industry, to be a potent regulatory neuroendocrine substance in relation to hair growth, hair color and hair cycle, depending on light periods, seasonal rhythms, environmental factors and reproductive rhythms. Nevertheless, the biological mechanisms of this extremely versatile hormone, especially with regard to human hair follicles, are not fully understood. In recent years, however, essential knowledge has been gained on the melatoninergic system of the skin, melatonin levels in keratinocytes and hair follicles, extrapineal intrafollicular melatonin synthesis and noradrenalin-induced increase in synthesis, as well as hair cycle-dependent expression of the membrane-bound melatonin receptor MT2 and the nuclear receptor RORalpha. Functional data on the growth of human hair both in vitro and in vivo show that melatonin might play an essential role in hair physiology.

Piecing together the pigment-type switching puzzle

285, 2370–2375. Griffin, B.P., and Topol, E.J. (2009). Manual of Cardiovascular Medicine (Philadelphia, PA: Lippincott Williams & Wilkins). Haissaguerre, M., Jais, P., Shah, D.C., Takahashi, A., Hocini, M., Quiniou, G., Garrigue, S., Le Mouroux, A., Le Metayer, P., and Clementy, J. (1998). Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N. Engl. J. Med. 339, 659– 666. Mjaatvedt, C.H., Kern, C.B., Norris, R.A., Fairey, S., and Cave, C.L. (2005). Normal distribution of melanocytes in the mouse heart. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 285, 748–757. Nichols Jr, S.E., and Reams Jr, W.M. (1960). The occurrence and morphogenesis of melanocytes in the connective tissues of the PET ⁄MCV mouse strain. J. Embryol. Exp. Morphol. 8, 24– 32. Ruskin, J.N., and Singh, J.P. (2004). Atrial fibrillation endpoints: hospitalization. Heart Rhythm 1, B31–B34, discussion B34–35. Yajima, I., and Larue, L. (2008). The location of heart melanocytes is specified and the level of pigmentation in the heart may correlate with coat color. Pigment Cell Melanoma Res. 21, 471–476.

Post‐Traumatic Tress Disorder: Obama, Palin and Marie‐Antoinette

Post‐Traumatic Tress Disorder: Obama, Palin and Marie‐Antoinette

Biological characteristics and functions of dermal papilla cells

Dermal papilla cells (DPC) play an essential role in embryonic formation of hair follicles, regulation of hair growth cycle and maintenance of hair growth. It has been proved that cultured DPC have the ability to induce hair follicle regeneration in vivo and in vitro. At the same time, DPC have obvious properties of adult stem cells. Biological characteristics and functions of DPC are a focus in hair follicle cell biology research, and to study into them will provide theoretical basis for the diagnosis and treatment of hair loss, construction of tissue engineering skin with hair follicles and stem cell-based tissue engineering research. Key words: Hair follicle; Dermal papilla cells; Stem cells; Biology

Circadian clock genes contribute to the regulation of hair follicle cycling.

Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK–regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.

A TR(I)P to Pruritus Research: Role of TRPV3 in Inflammation and Itch

Pruritus in eczema and other inflammatory skin diseases is an unsolved problem. Recent findings strongly indicate that histamine is not the only mediator of pruritus. Subtypes of the transient receptor potential (TRP) ion channel superfamily are expressed by sensory nerves, keratinocytes, and certain leukocytes. Temperature, pH changes, and certain toxins activate TRPs. New evidence indicates that the vanilloid type 3 (TRPV3) channel is crucially involved in pruritic dermatitis, making it a good candidate for future therapy in skin inflammation and pruritus.

Chemotherapy-Induced Alopecia

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

Pitx2, a β-catenin-regulated transcription factor, regulates the differentiation of outer root sheath cells cultured in vitro

Beta-catenin exerts its crucial role in hair follicle development and hair growth cycle. Although the importance of Wnt/beta-catenin is well recognized, the downstream effectors of beta-catenin have not been clearly elucidated yet. The aim of this study is to identify the beta-catenin-regulated genes in cultured human hair outer root sheath (ORS) cells. We transduced ORS cells with adenovirus harboring the expression cassette for constitutive active form of beta-catenin, then performed cDNA microarray. Overexpression of beta-catenin led to the upregulation of hair cell differentiation markers such as keratin 16 and 17. In addition, the expression of Pitx2, a bicoid-type homeodomain transcription factor, was also increased by overexpression of beta-catenin in ORS cells cultured in vitro. To investigate the potential role of Pitx2, we made the recombinant adenovirus expressing Pitx2, then transduced into the cultured ORS cells. Interestingly, Pitx2 induced the expression of keratin 16 and 17, indicating that Pitx2 activates ORS cells towards the follicular differentiation pathway preferentially. Our results implicate the potential importance of Pitx2 as a beta-catenin downstream modulator in hair growth control.

Silencing the androgen receptor: New skills for antiandrogen oligonucleotide skin and hair therapy

Hair growth and follicular cycle are regulated predominantly through androgens under complex genetic and hormonal control. Human hair growth occurs in cycles of three phases, anagen (continuous growth), catagen (cessation of growth) and telogen (resting phase). In genetically susceptible subjects, hair follicles in vertex and frontal regions of the scalp respond to androgens by reducing length of the anagen phase and regression of the follicles producing weaker and thinner hairs. More than 50% of men by the age of 50 years and women over 60 years suffer from androgenetic alopecia. The mesenchymal-derived dermal papilla cells (DPC) exert a control on the hair growth cycle, express androgen receptor, are responsive to androgen hormones and are implicated in triggering baldness in humans. Today, androgens are considered inhibiting hair follicle activity by early inducing catagen. Although the pathogenic mechanisms underlying androgenetic alopecia are not fully understood it is now accepted that androgens (mainly testosterone and dihydrotestosterone) inhibit hair follicle activity, probably by triggering the expression or repression of some genes (not yet identified) involving modification of DPC and epithelial cells relationship, thereby leading to the induction of programmed cell death. Consequently, the anagen length period shortens, favoring catagen and finally miniaturizing the follicle and thinning the hair [ 1 Inui S. Fukuzato Y. Nakajima T. Yoshikawa K. Itami S. Androgen inducible TGF-Beta 1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair. FASEB J. 2002; 16: 1967-1969 PubMed Google Scholar , 2 Brodland D. Muller S. Androgenetic alopecia (common baldness). Cutis. 1991; 47: 173-176 PubMed Google Scholar ]. Moreover, other skin disorders such as acne vulgaris, hirsutism and seborrhea are dependent or sensitive to the androgens action [ 3 Sinclair R. Male pattern androgenetic alopecia. BMJ. 1998; 317: 865-869 Crossref PubMed Scopus (156) Google Scholar , 4 Shaw J.C. Acne: effect of hormones on pathogenesis and management. Am J Clin Dermatol. 2002; 20: 3001-3015 Google Scholar ]. With this in view, the developing of new topical therapeutics aiming at down regulating or silencing the expression of the AR seems the right choice as current therapeutic strategies are not completely satisfactory in terms of clinical efficacy and potential secondary effects [ [5] Sawaya M. Shapiro J. Androgenetic alopecia, new approved and approved treatments. Dermatol Clin. 2000; 18: 47-61 Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar ].

Ferrous Ferric Chloride Stimulates the Skin Cell Function and Hair Growth in Mice

Ferrous ferric chloride (FFC) is a distinct form of aqueous iron composed of a complex of ferrous chloride and ferric chloride that participates in both oxidation and reduction reactions. The author's previous study showed that the supplementation of culture medium with FFC stimulated the proliferation and differentiation of keratinocytes and melanocytes in newborn mice. FFC also stimulated the proliferation of cultured human keratinocytes, fibroblasts, and melanocytes. However, it is not known whether FFC stimulates the proliferation and differentiation of mammalian skin cells as well as hair growth in vivo. To answer this question, FFC-containing skin lotions (FFC Super Essence Plain and Moisture Type, Akatsuka Co.) were painted on the dorsal skin of newborn C57BL/10JHir (B10) mice and tested for their proliferation- and differentiation-stimulating effects on keratinocytes, fibroblasts, and melanocytes as well as for their stimulating effects on the hair growth. This treatment stimulated the proliferation and differentiation of epidermal keratinocytes, dermal fibroblasts, and epidermal and dermal melanocytes in the skin as well as hair growth. From 2 to 3 weeks after birth B10 mice generally lose their hairs except those on the head at the telogen stage of the hair growth cycle due to the expression of the alopecia. The treatment with FFC lotions markedly inhibited the alopecia hair-loss. These results suggest that FFC can stimulate the proliferation and differentiation of keratinocytes, fibroblasts, and melanocytes in the skin as well as the hair growth, and, in addition, can inhibit the alopecia hair-loss.

Aging of the hair follicle pigmentation system.

Skin and hair phenotypes are powerful cues in human communication. They impart much information, not least about our racial, ethnic, health, gender and age status. In the case of the latter parameter, we experience significant change in pigmentation in our journey from birth to puberty and through to young adulthood, middle age and beyond. The hair follicle pigmentary unit is perhaps one of our most visible, accessible and potent aging sensors, with marked dilution of pigment intensity occurring long before even subtle changes are seen in the epidermis. This dichotomy is of interest as both skin compartments contain melanocyte subpopulations of similar embryologic (i.e., neural crest) origin. Research groups are actively pursuing the study of the differential aging of melanocytes in the hair bulb versus the epidermis and in particular are examining whether this is in part linked to the stringent coupling of follicular melanocytes to the hair growth cycle. Whether some follicular melanocyte subpopulations are affected, like epidermal melanocytes, by UV irradiation is not yet clear. A particular target of research into hair graying or canities is the nature of the melanocyte stem compartment and whether this is depleted due to reactive oxygen species-associated damage, coupled with an impaired antioxidant status, and a failure of melanocyte stem cell renewal. Over the last few years, we and others have developed advanced in vitro models and assay systems for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture which may provide research tools to elucidate the regulatory mechanisms of hair follicle pigmentation. Long term, it may be feasible to develop strategies to modulate some of these aging-associated changes in the hair follicle that impinge particularly on the melanocyte populations.

The role of activins and follistatins in skin and hair follicle development and function

Investigations of the signalling between epithelial and mesenchymal compartments of skin during hair follicle initiation in utero and hair cycling have revealed the importance of the TGFβ superfamily in ectodermal organogenesis and morphogenesis. In particular the activins, their receptors and binding proteins such as follistatin, have been shown to be important regulators of cell proliferation, differentiation and apoptosis in hair follicle initiation, hair cycling, normal skin homeostasis and wound healing. Transgenic mice lacking various components of the activin signalling pathways display varying ectodermal pathologies including altered pelage hair follicle initiation. This review summarises the activin signal transduction pathways and the interactions between activins and other TGFβ signalling systems during hair follicle formation, hair growth cycling, skin function and wound healing.

A PstI polymorphism at 3′UTR of goat POU1F1 gene and its effect on cashmere production

POU1F1 is a positive regulator for prolactin (PRL) whose metabolites may directly or indirectly affect some aspects of the hair growth cycle, therefore, POU1F1 gene is an important candidate gene for cashmere traits selection through marker-assisted selection (MAS). Hence, in this study, the PCR-RFLP method was applied to detect a T>C transition determining a PstI polymorphism at the 3'UTR of POU1F1 locus and evaluate its associations with cashmere traits in 847 Inner Mongolia White Cashmere goats. In the analyzed population, the allelic frequencies for the T and C alleles are 0.959 and 0.041, respectively and the genotypic frequencies are in Hardy-Weinberg equilibrium (P > 0.05). Moreover, significant statistical relationships between the PstI polymorphism of POU1F1 gene and goat cashmere yields were found (*P < 0.05). When compared with TC genotype, TT genotype was associated with superior cashmere yields in 2, 4, and 5 years old individuals, as well as with average cashmere yield. Hence, TT genotype is suggested to be a molecular marker for senior cashmere yield.

Human hair pigmentation – biological aspects

Skin and hair colour contribute significantly to our overall visual appearance and to social/sexual communication. Despite their shared origins in the embryologic neural crest, the hair follicle and epidermal pigmentary units occupy distinct, although open, cutaneous compartments. They can be distinguished principally on the basis of the former's stringent coupling to the hair growth cycle compared with the latter's continuous melanogenesis. The biosynthesis of melanin and its subsequent transfer from melanocyte to hair bulb keratinocytes depend on the availability of melanin precursors and on a raft of signal transduction pathways that are both highly complex and commonly redundant. These signalling pathways can be both dependent and independent of receptors, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. Despite many shared features, follicular melanocytes appear to be more sensitive than epidermal melanocytes to ageing influences. This can be seen most dramatically in hair greying/canities and this is likely to reflect significant differences in the epidermal and follicular microenvironments. The hair follicle pigmentary unit may also serve as an important environmental sensor, whereby hair pigment contributes to the rapid excretion of heavy metals, chemicals and toxins from the body by their selective binding to melanin; rendering the hair fibre a useful barometer of exposures. The recent availability of advanced cell culture methodologies for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture should provide the research tools necessary to elucidate the regulatory mechanisms of hair follicle pigmentation. In the longer term, it may be feasible to develop hair colour modifiers of a biological nature to accompany those based on chemicals.

Hair growth promoting activity of Eclipta alba in male albino rats

Alopecia is a dermatological disorder with psychosocial implications on patients with hair loss. Eclipta alba Hassk. is a well-known Ayurvedic herb with purported claims of hair growth promotion. In the reported work attempts were undertaken to evaluate petroleum ether and ethanol extract of E. alba Hassk. for their effect on promoting hair growth in albino rats. The extracts were incorporated into oleaginous cream (water in oil cream base) and applied topically on shaved denuded skin of albino rats. The time (in days) required for hair growth initiation as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as positive control for comparison. Hair growth initiation time was significantly reduced to half on treatment with the extracts, as compared to control animals. The time required for complete hair growth was also significantly reduced. Quantitative analysis of hair growth after treatment with petroleum ether extract (5%) exhibited greater number of hair follicles in anagenic phase (69 +/- 4) which were higher as compared to control (47 +/- 13). The result of treatment with 2 and 5% petroleum ether extracts were better than the positive control minoxidil 2% treatment.

Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocyte-lineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.

Spaying‐induced coat changes: the role of gonadotropins, GnRH and GnRH treatment on the hair cycle of female dogs

Although spaying can result in qualitative hair coat changes in dogs, the influence of spaying on the hair growth cycle has never been described. The study aims were to examine the effect of spaying and gonadotropin-releasing hormone (GnRH) treatment on canine hair coat, cycle stages of hair follicles, plasma gonadotropin concentrations and mRNA transcription of luteinizing hormone (LH) and GnRH receptors in hair follicles. Fifteen female dogs were examined before and 1 year after spaying and 24 spayed dogs before and after GnRH treatment. Spaying resulted in increased plasma gonadotropin concentrations and increased anagen : telogen ratio of hair follicles, but only 20% of the dogs developed coat changes. No differences were found in mRNA transcription of LH and GnRH receptors. GnRH treatment resulted in reduced plasma gonadotropin concentrations and improvement of coat changes in 79% of patients. This was associated with an increase in catagen hair follicles without changes in the anagen : telogen ratio. The present study demonstrated that spaying had an effect on the anagen : telogen ratio of hair follicles. Spaying-induced coat changes did not correlate with the anagen : telogen ratio. GnRH treatment reduced gonadotropin concentrations and reversed coat changes in some dogs, but had no effect on the hair growth cycle other than increasing the number of catagen hair follicles. A weak positive correlation between the plasma LH concentration and the anagen : telogen ratio was noted; however, our data did not suggest a direct receptor-mediated hormonal effect on the hair follicle. The present study did not identify the pathomechanism of spaying-induced coat changes.

Idiopathic hirsutism: excessive bodily and facial hair in women

Hirsutism is the excessive and increased bodily and facial hair growth in women in locations where hair is normally minimal or absent. It refers to the growth of hair in a pattern normally occurring only in men, and therefore primarily raises psychological, cosmetic and social concerns. Idiopathic hirsutism (IH), where the cause of excessive hair growth is unknown, is considered to be the most common form of hirsutism. It is suspected that this type of hirsutism may be familial, as there is often a family history of the condition. Women with IH will generally have normal menses and normal levels of testosterone. There are many treatment modalities that fall into two broad groups: medical and mechanical treatment. An example of a medical treatment is when an agent is used, which interferes with the synthesis of androgen at the ovarian or adrenal level, or by inhibiting the effect of androgen at the receptor level. An example of a mechanical treatment is laser hair removal, where the hair follicle is destroyed; however, much depends on the on the skill of the treating practitioner, laser type, laser spot size, skin type, hair colour, and the stage at which the hair follicles were during their hair growth cycle, and the delivered wavelength. Laser offers the fastest method of hair loss. Other mechanical treatments include electrolysis, depilatory creams, plucking and waxing. This article presents a general overview of IH, including a definition, diagnostic measures, clinical manifestations, normal and abnormal physiology, and treatment options.

Tissue Inhibitor of Metalloproteinases-3 Promoter Methylation is an Independent Prognostic Factor for Bladder Cancer

TIMP-3 (tissue inhibitor of metalloproteinases-3) is 1 of 4 members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases. We analyzed TIMP-3 methylation in 175 urine sediment DNA samples from patients with bladder cancer with well characterized clinicopathological parameters, including patient outcome. We examined urine sediment DNA for aberrant methylation of 9 genes, including TIMP-3, by quantitative fluorogenic real-time polymerase chain reaction. Using an optimal cutoff value by TaqMan(R) quantitation we found that the risk of death was statistically significantly higher in patients with higher TIMP-3 and ARF methylation (HR 1.99, 95% CI 1.12 to 3.27, p = 0.01 and HR 1.66, 95% CI 1.00 to 2.76, p = 0.05, respectively) than in patients without/lower TIMP3 and ARF methylation in urine. A significant correlation was also seen between the risk of death and stage 3 tumor (HR 2.73, 95% CI 1.58 to 4.72, p = 0.003) and metastasis (HR 3.32, 95% CI 1.98 to 5.57, p = 0.0001). Multivariate analysis subsequently revealed that TIMP-3 methylation was an independent prognostic factor for bladder cancer survival with stage and metastasis (p = 0.001 and 0.02, respectively). These results suggest that TIMP-3 promoter methylation could be a clinically applicable marker for bladder cancer progression.

Influence of TRPV3 mutation on hair growth cycle in mice

We recently reported that Gly573Ser substitution of the transient receptor potential cation channel, subfamily V member 3 (TRPV3) caused hair loss in DS- Nh mice. To further elucidate the effects of this mutation on the development of the spontaneous hairless phenotype, we examined the temperature–response to epidermal sheets from DS- Nh and DS mice. It was indicated that the mutation was gain-of-function. We also performed genetic and histological analyses with both strain skins. DNA microarray data revealed that the levels of keratin-associated protein 16-1, 16-3, and 16-9 genes related to the anagen phase were decreased in the skins of DS- Nh mice compared with those of three days old DS mice. Histological analysis revealed that the anagen phase persisted in DS- Nh mice, and that the telogen phase was seen in DS but not DS- Nh mice at 21 days of age. Regulation of TRPV3 appears to be important for appropriate hair development in rodents.