Soluble and insoluble collagen and elastin in the rat hair cycle

Summary Soluble and insoluble collagen and elastin were chemically evaluated in the dorsal skin of rats during the third hair cycle.Both fractions of collagen remain unchanged during anagen, while they increase considerably in the first days of telogen to drop afterwards.Elastin content gradually increases throughout anagen and falls in telogen.The authors suggest that the increasing amounts of collagen in the first part of telogen may be responsible for the progressive block in the downwards movements of previously growing follicles into the dermis.Elastin data could be the result of a mechanical readjustment of skin to the expansion provoked by growing follicles.     

Telogen skin contains an inhibitor of hair growth

We have investigated whether C57B1-6 mouse skin with all its follicles in the telogen stage of the hair cycle contains a hair-growth inhibitory activity, as opposed to skin with anagen follicles. Crude aqueous extracts of whole telogen mouse skin (TE), anagen skin (AE) or vehicle alone (V) were injected intraperitoneally into mice in which anagen had previously been induced by plucking of telogen hair follicles. Injection of TE, but not AE or V, significantly retarded the development of anagen follicles, as measured by macroscopic and quantitative microscopic hair growth parameters (skin pigmentation and thickness, appearance of trichohyaline granules) and the incorporation of tritiated thymidine into mouse skin from animals previously treated with either TE or V (skin organ culture). This inhibitory activity seemed to be localized to the epidermis and was also present in rat epidermis. We suggest that this apparently non-species-specific inhibitor present in telogen skin may play a role in regulating the hair cycle in rodents.     

Expression of the L-fucose moiety on infrainfundibular follicular keratinocytes of terminal follicles, its decreased expression on vellus and indeterminate follicles of androgenetic alopecia, and re-expression in drug-induced hair regrowth.

The distribution of various glycoprotein molecules on the surface of follicular keratinocytes was studied with a panel of lectins with specificity for various sugar moieties on biopsy specimens from both bald/balding scalp and normal occipital scalp, of 23 patients with androgenetic alopecia as well as on biopsies of normal forearm skin of four patients. The most significant differences between bald and normal scalp biopsy were noted with Ulex europaeus agglutinin I (UEA I). We noted an increased (91.8% +/- 3.1; mean +/- SE) expression of UEA I binding sites on the infra-infundibular follicular keratinocytes in anagen terminal scalp hairs, compared to 28.5% +/- 5.2 in the indeterminate (anagen) hairs of balding scalps, and 23.2% +/- 6.3 in the anagen follicles of vellus fore-arm hairs. By contrast, the telogen hairs demonstrated minimal UEA I staining: 4.0% +/- 0.8, mean +/- SE in telogen scalp hairs, 1.8% +/- 0.5 in telogen hairs of balding scalps (0% in completely bald scalps, in which all the hairs were in the telogen phase), and 1.9% +/- 0.2 in telogen forearm hairs. The percentage of UEA I staining correlated with the length of the infra-infundibular follicles in all cases studied. In three cases of hair regrowth after hair growth promotors, the UEA I staining increased to 80.6% +/- 6.1 in anagen hairs and correlated with increased length of infra-infundibular follicles. Our data indicate that there are 1) marked differences between anagen and telogen follicles in UEA I binding to infra-infundibular follicular keratinocytes; 2) the percentage of UEA I staining reflects the size (length) of the infra-infundibular hair follicle; and 3) the anagen follicles of balding scalps (indeterminate hairs) show UEA I staining resembling that exhibited by anagen follicles of vellus hairs.     

Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model

Latanoprost and isopropyl unoprostone, which are analogues of prostaglandin F2alpha (PGF2alpha), are promising drugs for the reduction of intra-ocular pressure. However, they have been reported to have side effects, including hypertrichosis and hyperpigmentation of the eyelashes and periocular skin, and occasionally poliosis. In order to investigate these effects further, PGF2alpha, latanoprost and isopropyl unoprostone were applied to the dorsal skin of 7-week-old C57BL/6 mice, and hair length was measured during the treatment. The three molecules all showed stimulatory effects on the murine hair follicles and the follicular melanocytes in both the telogen and anagen stages, and stimulated conversion from the telogen to the anagen phase. PGE2 is known to act synergistically with PGF2alpha, and hence the influence of PGE2 was also examined. PGE2 did not induce distinct telogen-to-anagen conversion, but showed moderate growth stimulatory effects on early anagen hair follicles. In addition, we observed a case of hypertrichosis and trichomegaly with an excess of melanogenesis, leading to the emergence of white hair, suggesting that poliosis can occur as a side effect of eye treatment with solutions of PGF2alpha analogues. The stimulatory effects of PGF2alpha and PGE2 on hair growth have been discussed with regard to the role of protein kinase C and mast cells.     

Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study

Summary Background We have previously reported that several selective protein kinase C (PKC) inhibitors, including procyanidin B‐2, promote hair epithelial cell growth and stimulate anagen induction. Objectives We discuss the hypothesis that the hair‐growing activity of procyanidin B‐2 is related to its downregulation or inhibition of translocation of PKC isozymes in hair epithelial cells. Methods We examined the effect of procyanidin B‐2 on the expression of PKC isozymes in cultured murine hair epithelial cells as well as PKC isozyme localization in murine dorsal skin at different stages in the hair cycle. Results We observed that procyanidin B‐2 reduces the expression of PKC‐α, ‐βΙ, ‐βΙΙ and ‐η in cultured murine hair epithelial cells and also inhibits the translocation of these isozymes to the particulate fraction of hair epithelial cells. Our immunohistochemical analyses demonstrated that PKC‐α, ‐βΙ, ‐βΙΙ and ‐η are specifically expressed in the outer root sheaths of both anagen and telogen hair follicles. The hair matrix at the anagen stage showed no positive staining for these PKC isozymes. Moderate to intense staining for PKC‐βΙ and ‐βΙΙ in the epidermis and hair follicles was observed in a telogen‐specific manner; however, expression of PKC‐α and ‐η during the telogen stage was not conspicuous. Gö 6976, an inhibitor of calcium‐dependent (conventional) PKC, proved to promote hair epithelial cell growth. Conclusions These results suggest that PKC isozymes, especially PKC‐βΙ and ‐βΙΙ, play an important role in hair cycle progression and that the hair‐growing mechanisms of procyanidin B‐2 are at least partially related to its downregulation of PKC isozymes or its inhibition of translocation of PKC isozymes to the particulate fraction of hair epithelial cells.     

Ber-EP4 antigen is a marker for a cell population related to the secondary hair germ

Ber-EP4 is an antibody to a cell membrane glycoprotein of unknown function. In the skin, Ber-EP4 immunoreactivity has been reported to be localized in structures composed of basaloid epithelial cells, i.e. fetal epithelial germ cells, basal cell carcinoma, and trichoepithelioma as well as eccrine or apocrine ducts. In this study, we further characterized the follicular expression of Ber-EP4 immunoreactivity at different stages of the hair cycle of human terminal hair follicles. In addition, to clarify the location of Ber-EP4(+) cells, we compared the Ber-EP4 immunoreactivity with the expression of keratin 15 and keratin 19. Positive staining by Ber-EP4 was found in the lower part of the epithelial strand of late catagen hair follicles, in the secondary hair germ of telogen hair follicles, and in the matrix of early anagen hair follicles but not in any parts of mature anagen hair follicles. In contrast, the follicular expression of keratin 15 detected by using LHK15 antibody was restricted to two distinct parts of anagen hair follicles, i.e. the outer root sheath above the hair bulb and that of the isthmus including the bulge area, and to the outer root sheath of late catagen and telogen hair follicles. The follicular expressions of keratin 19 and that of keratin 15 were apparently superimposed, whereas keratin 15 expression was more extended. The immunoreactivity of LHK15 antibody and antikeratin 19 antibody against the secondary hair germ of telogen follicles was negative or dim. Our results suggest that Ber-EP4 reacts with the secondary hair germ and possibly a cell population related to the secondary hair germ but not with the presumptive stem cell population as revealed immunohistochemically either by the keratin 15 or keratin 19 expression.     

Finasteride increases anagen hair in men with androgenetic alopecia

BACKGROUND: The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). OBJECTIVES: The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. PATIENTS/METHODS: Two hundred and twelve men, age 18-40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm(2) target area of the scalp. RESULTS: At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1.74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1.57. At week 48, the finasteride group had a net improvement (mean +/- SE) compared with placebo in total and anagen hair counts of 17.3 +/- 2.5 hairs (8.3% +/- 1.4%) and 27.0 +/- 2.9 hairs (26% +/- 3.1%), respectively (P < 0.001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0.001). In this study, treatment with finasteride 1 mg day(-1) for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. CONCLUSIONS: These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients.     

Exogen hair characterization in human scalp

BACKGROUND/AIM: Classically, the hair cycle is described as a sequence of three successive phases: a hair-growth phase named anagen, a regression phase or catagen and a resting phase or telogen. In rodents, it appears that the resting hair follicle population contains also a new phase that has been identified recently as the exogen phase of the hair cycle. This phase leads to the release of the telogen club and results in hair shedding. The aim of this paper is to propose a method that is applicable to humans and that is able to discriminate the two components of the resting hair population i.e. the telogen and the exogen hair follicles. METHODS: We used non-invasive approaches to entrap exogen scalp hair into silicon-based polymers. We also extracted growing and non-growing hair with a calibrated dynamometer. We characterized differences between anagen, catagen, telogen and exogen root ends with histochemical stains and with the scanning electron microscope. Furthermore, we documented all known hair-cycle stages with the contrast-enhanced phototrichogram (CE-PTG) technique. RESULTS: We demonstrated that anagen and telogen hair are firmly anchored to the hair follicle and that cohesion forces are correlated with hair thickness. On the contrary, exogen hair are passively retained within the hair follicle. Among the resting hair population, telogen clubs retain cellular elements of the outer root sheaths that are not found on exogen hair. The specificity of the new exogen collection method was documented with the simultaneous use of the CE-PTG method: indeed anagen, catagen and telogen follicles remain unaffected by the exogen extraction procedure. CONCLUSION: Exogen hair can be sampled specifically from the human scalp with a new non-invasive method. Our data suggest that the casual levels of exogen hair, in normal individuals and under the present experimental conditions, are usually less than seven hair per cm(2).     

Hair cycle control by leptin as a new anagen inducer

Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5‐week‐old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5‐week‐old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild‐type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22–56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild‐type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild‐type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT‐PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well‐known adipokine, acts as an anagen inducer and represents a new player in hair biology.     

Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte‐mediated growth inhibition of anagen‐phase vibrissa hair

Adipose tissue encircles the lower portion of anagen hair follicles and may regulate hair cycle progression. As leptin is a major adipokine, its level of expression from the dermal white adipose tissue during hair cycle progression was studied. The result shows that leptin level is differentially expressed during hair cycle, the lowest in early anagen phase, upregulated in late anagen phase and the highest in the telogen phase. On the other hand, leptin receptor is detected in keratin 15‐positive hair bulge epithelium of both anagen‐ and telogen‐phase hair follicles of mice pelage and vibrissa hair, and hair from human scalp. Leptin contributes to adipocyte‐mediated growth inhibition of anagen‐phase vibrissa hair as demonstrated in organ culture and coculture system. Our data suggest that leptin of dermal white adipose tissue might regulate hair growth and, therefore, hair cycle progression via leptin receptor on the hair follicle epithelium.     

CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling

Background  CD10 and CD34 have been detected in both epithelial and mesenchymal components of anagen human hair follicles.
Objectives  To analyse the expression of CD10 and CD34 in human hair follicle development as well as in different phases of the hair cycle.
Methods  Fetal and adult hair follicles at different stages of the hair cycle were examined by immunohistochemistry for CD10 and CD34.
Results  In fetal follicles, CD10 is expressed by the cells of the placodes, and CD34 by the mesenchymal cells of the dermal condensate. As the follicle matures, CD10 can be seen in the matrix cells, inner root sheath and dermal sheath. In adult follicles, the expression of CD10 in the follicular epithelium is present in anagen follicles, but tends to disappear in catagen, and is not detected in telogen. The CD10 positivity of the dermal sheath is more intense in catagen than in anagen follicles. CD34 immunostaining of the external root sheath was seen in adult anagen follicles but not in fetal follicles. This staining of the anagen outer sheath tends to disappear in catagen and is not detected in telogen.
Conclusions  CD10 and CD34 are not proteins constantly present in a specific cell type of the hair follicle, but are proteins that can be expressed by both epithelial and mesenchymal cells depending on the stage of development and hair cycle. The distribution of the immunoreactivity to CD10 in the placode and CD34 in the dermal condensate suggests a role of these proteins in initial stages of hair formation.     

The effect of topical minoxidil on hair follicular cycles of rats

To explore an easily accessible and reproducible model for examining the effect of minoxidil on hair growth, we studied the effect of minoxidil on the natural hair cycles of rats from birth to 80 days of age. During the 1st and 2nd postnatal cycles, the hair follicles grew very rapidly and the size of anagen follicles were markedly enlarged. In the 3rd cycle (50 days to approximately 100 days of age), duration of the telogen phase lasted approximately 20 days. Topical minoxidil, 1%, 3%, or 5% solution, applied on the backs of the rats from 23 days (weaning) to 80 days, induced a remarkable shortening of the telogen phase in the 3rd cycle. Although the dose-dependent response was very minimal, rats treated with 3% or 5% minoxidil showed similar effects in the 4th cycle. Minoxidil, however, did not induce prolongation of the anagen phase, but increased the rate of DNA synthesis in the anagen bulb during the 2nd and 3rd cycles. These results suggest that minoxidil specifically stimulates the secondary germ of the telogen follicles, resulting in rapid progression to anagen follicles.     

Intermittent foot shock stress prolongs the telogen stage in the hair cycle of mice

Stress significantly influences skin diseases and cutaneous functions. Recently, interactions between stress and skin conditions have been studied in animal models using various systemic stressors. Here, we studied the effect of intermittent foot shock stress on the hair cycle of C57BL/6 mice. After a 2-week period of intermittent foot shock stress, we examined the changes in the depilation-synchronized hair cycle macroscopically and histologically and we also measured the plasma levels of corticosterone. We found that foot shock stress prolonged the telogen stage and delayed the subsequent anagen induction in the hair cycle. The distribution patterns of corticotrophin releasing factor or corticotrophin releasing factor receptor positive cells in the skin of stressed or of control mice were identical with those in the ordinal hair cycle. It is noteworthy that corticotrophin releasing factor positive keratinocytes were observed in the telogen follicles of the stressed mice but were negative in the telogen follicles of the non-stressed mice in this study. Plasma corticosterone levels were significantly higher in the stressed group than in the control group. These results suggest that increased levels of plasma corticosterone may be involved in the mechanism underlying the stress-induced delay of the hair cycle.     

Effect of hair growth cycles on experimental cutaneous candidiasis in mice

Experimental cutaneous Candida albicans infections were produced in mice by inoculating the organisms onto areas of shaved flank skin where the hair follicles were in either the anagen (growing) or telogen (resting) phase of the growth cycle. Infection with Candida occurred in a majority of animals inoculated on either anagen or telogen skin, and the rate of clearance of the organisms was equivalent for infections on the 2 types of skin. Some of the animals inoculated on anagen skin developed foci of Candida infection in the well-developed hair follicles, below the skin surface. Deep foci of infection were not found after inoculation of the telogen areas. The infections resulted in increases in epidermal thickness and sensitization of the animals to Candida antigens, but these responses were not different between animals inoculated on the 2 types of skin. The results of these experiments indicate that although Candida albicans can infect skin containing either active or resting hair follicles, foci of infection below the skin surface occur only when well-developed hair follicles are present. These findings may have relevance to the consequences of human cutaneous candidiasis.     

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.     

Overexpression of skin protein kinase C-alpha in anagen hair follicles during induced growth of mouse hair

A role for protein kinase C (PKC)-alpha has been implicated in the growth of mouse hair. Topical application of PKC activators, hair plucking, allergic contact dermatitis and skin irritation can all enhance growth of mouse hair, and a significant increase in PKC-alpha level in whole mouse skin in mature anagen has been demonstrated in these processes. Overexpression of PKC-alpha in anagen hair follicles has also been reported in natural growth of mouse hair. It is known that overexpression of PKC-alpha is associated with the acceleration of cell growth. Therefore, we postulated that overexpression of PKC-alpha in mature anagen may relate to enhancement of hair growth. The distribution of PKC-alpha in hair follicles during induced growth of mouse hair has not previously been studied. In this study, hair growth in C57BL/6 mice was induced by plucking the telogen hairs on one side of the back. The undepilated contralateral side served as a control. Expression of PKC-alpha in hair follicles during the hair growth cycle induced was evaluated by immunohistochemistry using cryosections and a specific polyclonal anti-PKC-alpha immunoglobulin G (IgG) antibody. No PKC-alpha was detected in telogen hair follicles or in the hair follicles at 1 day post-depilation, when the induced hair cycle was in early anagen. At 4 days after plucking, when the induced hair cycle was in mid-anagen, intense staining for PKC-alpha was found in hair papillae. At 10 and 17 days after depilation, when the induced hair cycle was in mature anagen and early catagen, respectively, all outer root sheath (ORS) cells and outer connective sheaths of hair follicles were stained positive. Because no PKC-alpha was detected in telogen hair follicles in this study, down-regulation of PKC-alpha in early anagen could not be observed. However, consistent with our previous findings, overexpression of PKC-alpha was found in mid-anagen and mature anagen. As overexpression of PKC-alpha has been shown to be associated with acceleration of cell growth, our results support the notion that PKC-alpha may play an important role in growth of hair follicle cells in induced growth of hair. As PKC levels are known to increase in hyperglycaemia, overexpressed PKC-alpha in mature anagen hair follicles may be related to the putative function of the ORS in mobilizing glycogen stores for anagen growth.     

Interleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed factor with hair growth inhibitory properties

Abstract:  The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the interleukin (IL)-6 cytokine family. We examined members of this family for their expression and activity in hair follicles. Quantitative polymerase chain reaction using mRNA derived from microdissected, anagen-stage human hair follicles and comparison to non-follicular skin epithelium revealed higher levels of IL-6 (15.5-fold) and oncostatin M (OSM, 3.4-fold) in hair follicles. In contrast, expression of all mRNAs coding for IL-6 cytokine family receptors was reduced. Immunohistology suggested expression of OSM, gp130, leukaemia inhibitory factor receptor (LIFr) and IL-11r in the hair follicle root sheaths and dermal papilla, while IL-11, IL-6r and OSMr were expressed in root sheaths alone. IL-6 was expressed in the dermal papilla while cardiotrophin-1 (CT-1) and LIF were not observed. OSM and to a lesser extent CT-1 exhibited a dose-dependent growth inhibition capacity on human hair follicles in vitro . OSM and CT-1 incubated with agarose beads and injected subcutaneously at 1 μg per mouse into telogen skin of 65-day-old mice revealed no capacity to induce anagen hair growth. In contrast, injection of 65-day-old mice in which anagen had been induced by hair plucking revealed a moderate hair growth inhibitory capacity for OSM, but no significant effect for CT-1. The data identify OSM as a modulator of hair follicle growth and suggest other family members may also have some degree of hair growth inhibitory effect. In principle, increased expression of some IL-6 cytokine family members in cutaneous inflammation might contribute to the promotion of hair loss.     

Regulation of Hair Shedding by the Type 3 IP(3) Receptor

Here we showed that the type 3 IP(3) receptor (IP(3)R3) is specifically expressed in hair follicles of the skin and plays an important role in the regulation of the hair cycle. We found that IP(3)R3-deficient (Itpr3(-/-)) mice had prominent alopecia, which was characterized by repeated hair loss and regrowth. The alopecic stripe runs along the body axis like a wave, suggesting disturbed hair-cycle regulation. Indeed, the hair follicles of the alopecic region were in the early anagen stage. Although the hair growth and proliferation activity of the hair matrix cells in the anagen phase were normal in Itpr3(-/-) mice, telogen club hairs in the telogen-anagen transition phase were loosely attached to the hair follicles and were easily removed in contrast to the more tightly attached club hairs of Itpr3(+/+) mice. Itpr3(-/-) keratinocytes surrounding the telogen club hairs have sparse cytokeratin filaments extending in random directions, as well as less developed desmosomes. Furthermore, nuclear factor of activated T cells c1 (NFATc1) failed to translocate into the nucleus of keratin 6-positive bulge cells in Itpr3(-/-) telogen follicles. We propose that hair shedding is actively controlled by the IP(3)R3/NFAT-dependent signaling pathway, possibly through the regulation of cytokeratin filaments in keratinocytes.     

Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles

We quantified the mRNA expression of all 22 fibroblast growth factor family members (FGF) and their four receptors (FGFR) in adult mouse full-thickness skin at various stages of the hair growth cycle. We found that in addition to mRNA encoding FGF previously identified in skin (FGF1, 2, 5, 7, 10, 13, and 22), FGF18 mRNA was also strongly expressed. Expression of these FGF varied throughout hair growth cycle: mRNA expression of FGF18 and 13 peaked at telogen; FGF7 and 10 at anagen V; and FGF5 and 22 at anagen VI. In situ hybridization revealed that FGF18 mRNA is mainly expressed in the anagen inner root sheath and telogen bulge of hair follicles. In culture, FGF18 stimulated DNA synthesis in human dermal fibroblasts, dermal papilla cells, epidermal keratinocytes and vascular endothelial cells. When FGF18 was administered subcutaneously to mice in a uniform telogen state, anagen hair growth was observed. Our findings suggest that FGF18 is important for the regulation of hair growth and the maintenance of skin in adult mice.