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Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption

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Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption

Abstract

The stress hormone, cortisol, is known to affect the function and cyclic regulation of the hair follicle. When cortisol is present at high levels it has been demonstrated to reduce the synthesis and accelerate the degradation of important skin elements, namely hyaluronan and proteoglycans by approximately 40%. The following discussion outlines the relationship between stress, cortisol, and the effect on the normal function of the hair follicle. As a result of this connection, important correlations have been established in the literature to form a basis for novel, effective treatments of stress-related hair growth disorders. Amongst various treatment methods and substances, oral supplementation with a specific bioavailable proteoglycan stands out as a promising new therapeutic treatment method. J Drugs Dermatol . 2016;15(8):1001-1004.
A  1001 V  • I 
C ©  ORIGINAL ARTICLES J  D  D
SPECIAL TOPIC
Stress and the Hair Growth Cycle: Cortisol-Induced
Hair Growth Disruption
Erling Thom PhD
ETC Research and Development; Oslo, Norway
The stress hormone, cortisol, is known to affect the function and cyclic regulation of the hair follicle.
When cortisol is present at high levels it has been demonstrated to reduce the synthesis and accelerate the degradation of important
skin elements, namely hyaluronan and proteoglycans by approximately 40%.
The following discussion outlines the relationship between stress, cortisol, and the effect on the normal function of the hair follicle. As
a result of this connection, important correlations have been established in the literature to form a basis for novel, effective treatments
of stress-related hair growth disorders.
Amongst various treatment methods and substances, oral supplementation with a specic bioavailable proteoglycan stands out as a
promising new therapeutic treatment method.
J Drugs Dermatol. 2016;15(8):1001-1004.
ABSTRACT
INTRODUCTION
Biological organisms are continuously exposed to a myr-
iad of internal and external stimuli and stressors. As a
response to these stimuli, living organisms have devel-
oped natural defence and adaptation mechanisms over time.
Stress is a common stimulus and well-known causal factor of
hair growth disorders and hair loss. The link between psycho-
emotional stress and hair loss can be distinguished according
to three levels of interaction.1
Interaction Level 1: Acute or Chronic Stress as a Primary In-
ducer of Telogen Efuvium
Telogen efuvium is one of the major hair growth disorders and
is closely related to stress. Occurring mainly in women, telogen
efuvium can be induced as a result of stress or extreme hor-
monal imbalance. This creates a disruption to the normal hair
growth cycle in which anagen (growing) hairs prematurely en-
ter the telogen (resting) phase. Consequently, symptoms begin
to appear in the form of short, sudden bouts of hair shedding
with little to no hair growth.2
Interaction Level 2: Acute or Chronic Stress as an Aggravating
Factor in Hair Loss Disorders Whose Primary Pathogenesis is
of Endocrine, Toxic, Metabolic, or Immunological Nature (eg,
androgenetic alopecia, alopecia areata)
Androgenetic alopecia is the most common hair growth dis-
order in women and men. The large majority of hair growth
disorders occur due to a change in the hair growth cycle, which
is usually androgen dependent and genetically determined. In
the case of androgenetic alopecia, testosterone is converted to
dihydrotestosterone (DHT) via 5α-reductase. DHT then binds
to androgen receptors in the hair follicle, which results in the
shortening of the anagen phase and simultaneous prolongation
of the telogen phase, combined with hair follicle miniaturisa-
tion. Symptoms of hair thinning and loss result from a gradual
reduction in hair diameter and a visibly widened hair parting.3,4
Alopecia areata is an autoimmune disorder that affects men and
women equally. It is thought that the development of alopecia
areata may occur as a result of an environmental inuence on
the immune and hormonal microenvironments of the hair follicle.
Representing approximately 0.7% to 3.8% of all patients attending
dermatology clinics, alopecia areata is characterised by delimited
patches of hair loss on the scalp. Hair loss symptoms in this con-
nection can become more widespread, with complete loss of hair
on the scalp; alopecia totalis, or by a complete loss of all hair on
the scalp and body; alopecia universalis. Moreover, people with
alopecia areata may experience a reduced expression of glucocor-
ticoids due to weak response to acute physiological stressors.5.6
Interaction Level 3: Stress as a Secondary Problem in Re-
sponse to Prior Hair Loss
Stress resulting as a consequence of hair loss, in contrast to be-
ing a primary inducer or aggravating factor, can lead to further
perpetuation of hair loss. This may be due to a vicious cause-and-
effect circle arising between stress-as-response and hair fall.7
Stress and the Hair Follicle
The role and function of the hair follicle is sophisticated.
Through the continuous, cyclic production of hair bres, the
follicle serves as a sensory organ as well as an instrument of
psychosocial communication and protection in humans. This is
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A 2016 • V 15 • I 8
E. Thom
proteoglycans) by approximately 40%.18 As proteoglycans and
hyaluronan serve the function of attracting and retaining moisture
in the skin, the degradation and reduction of these skin compo-
nents would present as excessively dry skin.12
One known cortisol inhibitor is ketoconazole, an imidazole anti-
fungal agent used to treat dandruff and seborrheic dermatitis.
The functionality of ketoconazole has been indicated in vivo,
and consequently conrmed in vitro, to inhibit the secretion of
cortisol. This is done by blocking 11 beta-hydroxylase activity
which is then compensated by high levels of adrenocorticotrop-
ic hormone in vivo.19
Researchers have studied the effect of using a 2% ketoconazole
shampoo long-term, and it was demonstrated that the size and
proportion of hair follicles in the anagen phase, as well as hair
density, were improved in the case of androgenetic alopecia.
The 2% ketoconazole shampoo was also shown to have an addi-
tive effect for androgenetic alopecia when used in combination
with nasteride.20 The positive effect of this 2% ketoconazole
shampoo was later conrmed in a small, open study in which it
was concluded that ketoconazole may exert its positive effects
on androgenetic alopecia in both an androgen-dependent, as
well as androgen-independent manner.21
Proteoglycans and Cortisol
For the hair follicle to function properly according to a normal
cycle, specialised cells in the follicle must interact according
to intricate signalling mechanisms. A number of research stud-
ies conducted between 1991 and 2008 demonstrated that the
presence of proteoglycans and glycosaminoglycans play an
important role on the normal function and cycling mechanism
of the hair follicle.22-28
Proteoglycans are heavily glycosylated proteins that consist of
a core protein, together with one or more covalently attached
glycosaminoglycan side chains. Glycosaminoglycans are long,
unbranched polysaccharides containing a repeating disaccharide
unit.29
Specically, versican is a type of large proteoglycan belonging
to the lectican family, and is known as a chondroitin sulfate pro-
teoglycan. Versicans are present in a range of human tissues
and comprise one of the main components of the extracellular
matrix. This is to provide a loose and hydrated matrix during
key events in development and disease. Versicans are known
for their role in cell adhesion and are centrally involved in tis-
sue morphogenesis and maintenance. In addition, versicans
contribute to the development of a number of pathologic pro-
cesses including hair follicle cycling.30
Decorin is a proteoglycan from the small leucine-rich pro-
teoglycan gene family, and consists of a protein core with
done as the hair follicle functions according to an independent
growth mechanism called the Hair Growth Cycle. This all im-
portant Hair Growth Cycle is comprised of three phases; rapid
growth (Anagen), apoptosis driven regression (Catagen), and
relative inactivity or rest (Telogen).3
After a period of acute or chronic stress many individuals will
experience an increased amount of hair loss. In murine stud-
ies, chronic stress was signicantly associated with hair growth
inhibition, increased granulation of mast cells and perifollicular
inammation.8 Further studies, both in vitro and in vivo, have
demonstrated that certain stress-mediating substances such as
substance P, adrenocorticotropic hormone, prolactin, and corti-
sol actually inhibit the growth of hair.9-11
Neural signals have also been demonstrated to modulate hair
growth, however this is not essential for the normal function of
the hair growth cycle. Moreover, researchers have shown the
ability of corticotropin-releasing hormone to directly stimulate
isolated hair follicles in humans, with cortisol synthesis and
neuroendocrine feedback loops.1
Of particular interest are the steroid hormones cortisone and
cortisol, which are released in response to stress. As the re-
search cited above posits the direct effect of cortisol on the hair
follicle, a direct correlation between cortisol and the develop-
ment of hair loss can also be identied.
Cortisol and Cortisol Inhibitors
Studies have indicated a range of side effects on the skin and
its structural components resulting from the presence of excess
cortisol.12 In fact, the presence of elevated levels of cortisol has
been demonstrated in both males and females with androge-
netic alopecia, compared to controls.13,14
Measuring the precise effect of cortisol on human connection
tissue is not a simple and straightforward task. ‘Hair analysis’,
however, is a common method used to measure the presence
of external compounds in the body, especially in relation to il-
licit or harmful chemical substances.15 Hair analysis is widely
used since the presence of substances in the hair can be tracked
over time, due to the fact that hair grows at a steady rate of ap-
proximately 1 cm per month.16 Similarly, this methodology is
being applied to measure chronic stress in the body by tracking
and quantifying cortisol levels as a biological marker in hair.17
When analysing cortisol measurements in the body, interestingly,
low cortisol levels have been shown to exert positive effects. Low
levels of cortisol actually stimulate, as well as slow the breakdown
of hyaluronan and proteoglycans by approximately 25%. How-
ever when cortisol is present at high levels the opposite is true,
as it has been shown to reduce the synthesis and accelerate the
breakdown of these structural skin components (hyaluronan and
© 2016-Journal of Drugs in Dermatology. All Rights Reserved.
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No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.
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E. Thom
in the body after oral intake, which has been demonstrated in
two studies.38,39 Thus, the intake of specic proteoglycans as a
‘proteoglycan replacement therapy’ via oral supplementation is
a logical and promising approach to improve the function and
cycling of the hair follicle.
Not only has it been shown that versican is able to protect cells
from oxidative stress-induced apoptosis, but decorin has also
been recognised for its anagen inducing properties.40 Accord-
ing to a recent publication, it was concluded that supplements
containing specic bioavailable proteoglycans to revitalise dys-
functional hair follicles have opened a new era on nutritional
factors that inuence hair loss. In this connection it was rec-
ommended that a specic proteoglycan replacement treatment
(Nourkrin® with Marilex® from Pharma Medico) containing spe-
cic lectican, leucine versican, and decorin, is benecial as a
baseline treatment for all hair loss types. This treatment is rec-
ommended both as a prophylactic and a therapy, and especially
in connection to stress-related hair loss cases.41,42
CONCLUSION
Stress can have a detrimental effect on intricate microbiological
systems in the body, and especially in relation to the hair fol-
licle. As a response to internal and external stressors, cortisol
is released in the body and can eventually build up to excess
levels, and studies have demonstrated the ability of cortisol to
degrade integral substances in the skin and extracellular ma-
trix, namely hyluronan and proteoglycans.
In this way, excess cortisol is therefore able to exert a disruptive
effect on the ne-tuned mechanism of the hair follicle, leading
to the development of hair growth disorders such as androge-
netic alopecia, alopecia areata and telogen efuvium.
These causal relationships have led to a new focus on devel-
oping pharmacological treatments for hair growth disorders
based on a proteoglycan replacement methodology. A pro-
teoglycan supplementation replacement treatment (Nourkrin®
with Marilex® from Pharma Medico) featuring versican and
decorin specically, can play a pivotal role in the induction
and prolongation of the anagen phase of the hair growth cy-
cle. In addition, these lectican and leucine proteoglycans have
been demonstrated to protect from stress-induced apoptosis
as well as to exert a synergistic effect to inhibit the activa-
tion and secretion of mast cells in combination with certain
avonoids.
In fact, a specic proteoglycan replacement therapy3 has been de-
nitively categorised as opening a new era on nutritional factors
that inuence the Hair Growth Cycle and hair loss. However going
forward people suffering from hair growth disorders will still re-
quire complex, comprehensive and careful management beyond
pharmacological treatment to alleviate clinical symptoms.
12 leucine-rich repeats and a glycosaminoglycan chain. Decorin
is documented to play a pivotal role in hair biology, as studies
suggest its ability to modulate cycling and morphogenesis of
the hair follicle, as well as acting as an anagen inducer.31,32
Although the hair follicle normally functions as a well-balanced
biological system, it can become destabilised due to a range
of internal and external factors and stimuli.33 Specically, high
concentrations of cortisol in the body are known to have a dam-
aging effect on proteoglycans in and around the hair follicle.10,18
Treating Stress-Related Hair Loss
Of late, new pharmacological solutions are becoming in-
creasingly recognised as serious treatments for stress-related
disorders in the body.
When available, certain corticotropin-releasing hormone receptor
antagonists could provide a treatment solution to skin conditions
induced or aggravated by stress. However, inhibiting the activa-
tion of mast cells is considered a more promising approach in the
literature. In this connection only a few clinically available mol-
ecules are known to be effective, although recent studies have
shown that some avonols, specically quercetin, can inhibit both
newly synthesised and pre-stored mediators from mast cells in hu-
mans.34 One study has already demonstrated synergistic efcacy
between such avonoids and chondroitin sulphate proteoglycans
to inhibit both the activation and secretion of mast cells.35
It is further argued in the literature that to treat stress-triggered
telogen efuvium, for example, effective pharmacological treat-
ment should entail prolonging the anagen phase of the hair
growth cycle.34 Anagen phase prolongation would help prevent
the onset of early catagen, which is crucial, as this is the central
mechanism of the telogen efuvium condition.
To achieve this effect, a number of approaches exist which
range from the traditional to the more alternative. Popular, tra-
ditional treatments for hair loss such as applying minoxidil to
the scalp, can achieve anagen prolongation via the opening of
potassium channels.36
On the other end of the spectrum, alternative therapies such as
‘music listening’ have also been shown to signicantly reduce
chronic stress levels by measuring the presence of cortisol in
the hair.37 Yet as recent research indicates, the presence of cer-
tain proteoglycans represent a constant element in a stable,
well-functioning hair follicle. Naturally, the relationship be-
tween proteoglycans and the hair follicle represents a potential
treatment which falls between the traditional and the alterna-
tive, and which appears to be both novel and effective.
Producing a viable pharmacological treatment in this connec-
tion would require the uptake and distribution of proteoglycans
© 2016-Journal of Drugs in Dermatology. All Rights Reserved.
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A 2016 • V 15 • I 8
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The specic proteoglycan replacement3 methodology further
indicates a strong clinical rationale for supplementation against
age-related hair growth disorders, as proteoglycan synthesis is
generally reduced as a function of age. Moreover, the effect of
topical 2% ketoconazole shampoo should be further researched
for its ability to inhibit the effects of excess cortisol in a safe
manner.
The treatment approaches described herein do not yet address
the concomitant psychological implications that arise as a re-
sult of stress-induced hair growth disruption. Several physical
stress-reducing activities have been shown to reduce cortisol
levels, and quite recently, listening to music has been shown to
signicantly reduce chronic stress levels, as measured by the
presence of cortisol through hair analysis.
It can therefore be concluded that addressing and treating the
psychological aspects of stress-induced hair growth disorders
justies an equally interesting and important area for future re-
search.
DISCLOSURES
The author has received Honoria fees as consultant for Pharma
Medico.
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AUTHOR CORRESPONDENCE
Erling Thom
E-mail:................……........................................... erlingthom@etc.as
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... Most hair growth disturbances are related to changes in hair follicle cycling. For example, androgenetic alopecia and telogen effluvium are attributed to the shortening of the anagen phase and the continuing of the telogen phase of the hair follicle (Cho et al. 2010;Cutrer and Pittelkow 2006;Hadshiew et al. 2004;Siebenhaar et al. 2007;Thom 2016). ...
... Individuals with hair loss suffer from psychological problems and carry a sociocultural burden. It is common in both men and women; thus, many people are affected and suffer from psychological atrophy (Hadshiew et al. 2004;Thom 2016). In general, the causes of hair loss in humans include genetics, aging, the effects of drugs, psychological stresses, and sequelae after a disease or disease treatment. ...
... In general, the causes of hair loss in humans include genetics, aging, the effects of drugs, psychological stresses, and sequelae after a disease or disease treatment. From a biochemical and physiological point of view, hair loss has three main causes, i.e., excessive activity of male hormones, problems with scalp blood circulation, and a lack of nutrients essential for hair metabolism (Hadshiew et al. 2004;Thom 2016;Krause and Foitzik 2006;Shin et al. 2016;Peters et al. 2006Peters et al. , 2007. However, in recent years, the number of people suffering from hair loss due to changes in their diet or social environment and increased stress is increasing. ...
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We analyzed the effect of botulinum toxin (BTX) type A on the regeneration of hair follicle cells under continuous stress conditions. Thirty 6-week-old C57BL/6 mice were used, and hair loss was induced on their backs (10 control (CTL) mice, reared under normal conditions without stress; 10 mice, exposed to continuous stress (STRESS) by fixing in an enclosed space; 10 BTX + STRESS mice, injected subcutaneously with 1 IU of BTX (0.1 cc) where the hair follicles were removed under the same stress conditions). There was less hair growth in the STRESS and BTX + STRESS groups compared to that in the CTL group at 2 weeks. At 3 weeks, the telogen stage was mainly observed in the STRESS group whereas the anagen stage was observed in the CTL and BTX + STRESS groups. A substantial increase in terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was observed in the STRESS group compared to that in the CTL and BTX + STRESS groups. Substance P (SP) immunoreactivity cell levels increased in the STRESS group at 2 and 3 weeks compared to those in the BTX + STRESS group. SP expression increased at 2 and 3 weeks in the STRESS group compared to that in the CTL and BTX + STRESS groups. A delay in the regeneration cycle of the hair follicle cells occurred when stress was applied, and an almost normal regeneration cycle occurred when BTX was injected subcutaneously. Therefore, BTX may be a positive indicator for hair loss treatment.
... 16,17 High blood cortisol concentration has been reported as a major cause of chronic diseases such as obesity, body shape change, hypertension, diabetes, and hair loss. [18][19][20][21] It is important to research and develop natural products that can safely address various causes of menopause; over the past 15 years, our research team has tested several natural substances for this purpose. It has been found that MS-10 Ò , a natural thistle and thyme complex extract, safely modulates the activity of its receptors, efficiently utilizing the reduced estrogen. ...
... Cortisol is a stress hormone that causes various health problems such as stress, nervousness, obesity, and chronic diseases. [19][20][21] The results indicating PWI improvement with MS-10 intake are closely correlated with the results of lower cortisol concentration. In other words, insomnia, irritation, depression, and pain, which are physical and mental stress symptoms experienced by women, were effectively improved due to the improvement of cortisol. ...
Article
We evaluated the efficacy and safety of MS-10® for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index. MS-10 treatment effectively improved the symptoms by ∼48%. In addition, the quality of life of the women improved by 36% from four perspectives: vasomotor, psychosocial, physical, and sexual symptoms as evaluated using the menopause-specific quality of life (MenQoL) questionnaire. Our results show that MS-10 improves insulin-like growth factor-1 (IGF-1) and estrogen utilization through receptor activation, which are thought to have causative therapeutic effects on menopause and aging inhibition in women. Improvement of Enthotheline-1 (ET-1) in the blood after MS-10 intake led to an improvement in menopausal vascular symptoms. Improvements in bone formation and absorption markers such as osteocalcin, bone-specific alkaline phosphatase (BSALP), C-telopeptides of type I collagen (CTx), deoxypyridinoline (deoxyPYD), and N-telopeptides of type I collagen (NTx) in blood or urine indicate that MS-10 fundamentally improves bone health in women. By confirming the improvement of the psychological well-being index based on the improvement of stress hormone cortisol, MS-10 can solve causative psychological and physical stress-related symptoms. Moreover, various safety tests, such as those for female hormones, were confirmed. Therefore, it can be confirmed that MS-10 is a natural pharmaconutraceutical that causatively and safely improves health of women and aids in antiaging processes.
... Due to numerous anagen terminating signals induced by the virus, TE associated with COVID-19 is likely to be of an "immediate anagen release" kind with substantial loss of club hairs [42]. By influencing follicular stem cells and mis-regulating the metabolism of follicular proteoglycans, elevated cortisol, and catecholamine levels are said to change the hair growth cycle [43,44]. Perifollicular inflammation manifested by activated macrophage clustering and mast cell degranulation was observed in subjects experiencing psychological stress [40]. ...
... Another factor that deserves consideration is the role of increased cortisol under the conditions of COVID-19 [54]. High cortisol levels relate to the increased degradation of matrix proteoglycans and is, therefore, considered a disruptor of the hair growth cycle [43]. In summary, both biological and psychological factors play distinct roles in driving TE in COVID-19 survivors. ...
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The diffusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inducing coronavirus disease 2019 (COVID-19) has increased the incidence of several dermatological disorders, including hair loss (HL). This article aims to review the literature regarding the incidence of HL and telogen effluvium (TE) in COVID-19 patients and critically appraise the available evidence regarding the role of regenerative strategies like Platelet-Rich Plasma (PRP) and Human Follicle Stem Cells (HFSCs). A literature review regarding the correlation of HL and TE in COVID-19 patients analyzing the biomolecular pathway involved and the role of regenerative strategies was performed using PubMed, MEDLINE, Embase, PreMEDLINE, Scopus, and the Cochrane databases. Observational studies revealed an escalated incidence of pattern HL and TE in COVID-19 patients. Psychological stress, systemic inflammation, and oxidative stress are potential culprits. Proinflammatory cytokines and stress hormones negatively affect the normal metabolism of proteoglycans. Reduced anagenic expression of proteoglycans is a potential mediating mechanism that connects HL to COVID-19. Currently, only one study has been published on PRP against HL in COVID-19 patients. Further controlled trials are required to confirm PRP and HFSCs efficacy in COVID-19 patients.
... These proteins are important skin components, but also elements of the hair follicles and are essential for a normal hair follicle cycling and growth. 4 High levels of ACTH can also lead to overproduction of adrenal androgens, which in turn may further contribute to the CSrelated alopecia. Thus, hypercortisolism may impact the fine-tuned mechanisms of hair follicles resulting in hair growth disruption and hair loss. ...
... 5,14 The stress response is known to play an important role in hair loss pathology and is intrinsically linked to alopecia areata and telogen e uvium, with recent studies indicating that cortisol and microin ammation at the level of the hair follicle also plays a role in AGA. 5,15,16 Ashwagandha is a botanical that contains steroidal lactones which modulate and reduce cortisol levels. In a randomized, double-blind, placebo-controlled study of 98 patients, daily supplementation with 10% withanolide ashwaghanda showed statistically signi cant reductions in serum cortisol, serum C-reactive protein, blood pressure, and subjective feelings of stress compared to placebo. ...
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Background: Several oral nutraceuticals have recently emerged as products marketed to increase hair growth and thickness. However, these supplements typically lack the rigorous testing and statistically significant data that apply to pharmaceuticals. Therefore, the potential benefits of oral nutraceuticals for conditions of hair loss, such as androgenetic alopecia, have yet to be fully understood by dermatologists. Objective: The purpose of this article is to evaluate current studies in the literature to assess the efficacy of popular oral nutraceuticals marketed for hair growth in subjects with androgenetic alopecia. Methods: This article reviews the currently available literature on the nutraceuticals Nutrafol® and Viviscal® for hair growth and describes and evaluates the results observed. Results: Oral nutraceuticals are effective to a modest degree in promoting hair growth in men and women with androgenetic alopecia. Conclusion: Oral nutraceuticals have demonstrated efficacy in promoting modest hair growth in men and women with androgenetic alopecia and may serve as useful adjuncts to current treatments. As the popularity of nutraceuticals grows, it is important for dermatologists to be knowledgeable of the potential benefits and pitfalls of these supplements to appropriately counsel patients seeking treatment for hair loss.
... Stress related hormones such as glucocorticoids have negative effects both on skin and hair. Sustained exposure to cortisol leads to the atrophy of skin tissue mainly through extracellular matrix degradation, and increased levels of cortisol have been associated with hair growth disorders [1,2]. In skin, cortisone is converted intracellularly into its active form cortisol (hydrocortisone) by 11beta-hydroxysteroid dehydrogenase-1 (11βHSD1) [3] (Fig. 1) and the expression of this enzyme is increased by glucocorticoid treatments through a positive feedback loop [4]. ...
Article
Background: Lagerstroemia indica (L. indica) is reported to have diverse biological activities including anti-inflammatory, anti-cancer, neuro-regulatory, antidiabetic and antioxidant activity. Aims: The purpose of the present study is to examine the potential of hair growth promotion and/or hair loss prevention by L. indica extract. Patients/methods: The effects of L. indica on hair growth have been studied in human hair follicle dermal papillary (hHFDP) cells and follicular organ culture ex vivo by cell proliferation assay, PCR, western blot analysis and reporter gene activity assay. Moreover, a clinical trial was conducted in healthy volunteers. Results: L. indica significantly promoted the proliferation of hHFDP cells, which was associated with increased expression of TCF/LEF, VEGF and Gli1 mRNA, and inhibition of STAT6 and Smad2 mRNA. Treatment with L. indica also increased the TCF/LEF reporter gene activity but downregulated the SBE- and STAT6-luciferase activities. The expression of total β-catenin, CDK4 and CDK2 were elevated, while that of STAT6 and SMAD2/3 was suppressed upon treatment with L. indica. In human hair follicles organ culture, L. indica significantly inhibited hair follicular degeneration. The clinical trial showed a statistically significant rise in total hair count in test group (n=24) after 24 weeks of applying the hair tonic enriched with L. indica (141.46 ± 21.27 number/cm2 , p < 0.05). Conclusion: We suggest that L. indica extract prevents hair loss as well as stimulate hair growth by regulating the Wnt-β-catenin, JAK3-STAT6 and TGF-β1-Smad signaling pathways, and may be further developed as a novel functional cosmetic for preventing hair loss.
Article
Alopecia areata and depression tend to co-occur; however, their temporal association has not been comprehensively investigated. The aim of this study was to examine the temporal association between alopecia areata and depression. The study included only cases with a comorbid presentation of alopecia areata and depression (n = 1,936), extracted from the databases of the Clalit Health Services, Israel. Survival analyses were used to assess the cumulative probability of receiving alopecia areata as comorbid diagnosis in the years following depression, and vice versa, compared with the opposite trajectory. The results indicate that patients with alopecia areata had greater odds of subsequent depression within 2 years from alopecia areata diagnosis, and showed a steeper increase in cumulative probability of depression as time progressed (log-rank =336.38, p < 0.001), compared with the opposite trajectory. All patients with alopecia areata had comorbid depression within 10 years of alopecia areata, compared with 70% of depression patients receiving diagnoses of comorbid alopecia areata within the same time-frame.
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Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs). The HF is a unique "miniorgan" with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as "hair follicle immune privilege." The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN). IFN- γ is one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathogenesis of alopecia areata.
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Proteoglycans, a family of glycosaminoglycan (GAG) conjugated proteins, are important constituents of human skin connective tissue (dermis) and are essential for maintaining mechanical strength of the skin. Age-related alterations of dermal proteoglycans have not been fully elucidated. We quantified transcripts of 20 known interstitial proteoglycans in human skin and found that decorin was the most highly expressed. Decorin was predominantly produced by dermal fibroblasts. Decorin was localized in dermal extracellular matrix with GAG bound to type I collagen fibrils. Analysis of decorin extracted from young (21-30 years) and aged (>80 years) sun-protected human buttock skin revealed that decorin molecular size in aged skin is significantly smaller than in young skin. The average size of decorin protein did not alter, indicating size of GAG chain is reduced in aged, compared to young skin. This age-dependent alteration of decorin GAG may contribute to skin fragility of elderly people.
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The relation between music listening and stress is inconsistently reported across studies, with the major part of studies being set in experimental settings. Furthermore, the psychobiological mechanisms for a potential stress-reducing effect remain unclear. We examined the potential stress-reducing effect of music listening in everyday life using both subjective and objective indicators of stress. Fifty-five healthy university students were examined in an ambulatory assessment study, both during a regular term week (five days) and during an examination week (five days). Participants rated their current music-listening behavior and perceived stress levels four times per day, and a sub-sample (n=25) additionally provided saliva samples for the later analysis of cortisol and alpha-amylase on two consecutive days during both weeks. Results revealed that mere music listening was effective in reducing subjective stress levels (p=0.010). The most profound effects were found when 'relaxation' was stated as the reason for music listening, with subsequent decreases in subjective stress levels (p≤0.001) and lower cortisol concentrations (p≤0.001). Alpha-amylase varied as a function of the arousal of the selected music, with energizing music increasing and relaxing music decreasing alpha-amylase activity (p=0.025). These findings suggest that music listening can be considered a means of stress reduction in daily life, especially if it is listened to for the reason of relaxation. Furthermore, these results shed light on the physiological mechanisms underlying the stress-reducing effect of music, with music listening differentially affecting the physiological stress systems. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
Proteoglycans have been suggested to play pivotal roles in hair biology. Decorin is a prototypical member of the small leucine-rich proteoglycan family, which is involved in numerous biological processes. However, the role of decorin in the hair cycle has not been elucidated. Moreover, the effects of decorin on the activities of many growth factors are complex and it is hard to predict whether decorin would affect hair growth or the hair cycle positively or negatively. Jing et al. focused on the potential role of decorin in the hair cycle and found that decorin is highly expressed in the epidermis, in hair follicle epithelial cells and in dermal papilla cells in the anagen phase. The expression of decorin was decreased during catagen to telogen, except for the bulge region. Exogenous administration of decorin accelerated anagen and delayed catagen transition as a positive regulator of the hair cycle. Because TGF-β is one of androgen-induced pathogenic factors in androgenetic alopecia, this study provides clues to understand the pathogenesis and new therapeutic targets of hair loss. This article is protected by copyright. All rights reserved.
Article
Decorin is a prototypical member of the small leucine-rich proteoglycan (SLRP) family, which is involved in numerous biological processes. The role of decorin, as a representative SLRP, in hair follicle morphogenesis has not been elucidated. We present our initial findings on decorin expression patterns during induced murine HF cycles. It was found that: decorin expression is exclusively restricted to the epidermis, outer root sheath, and sebaceous glands during the anagen phase, which correlates with the upregulation of decorin mRNA and protein expression in depilated murine dorsal skin. Furthermore, we used a functional approach to investigate the effects of recombinant human decorin (rhDecorin) via cutaneous injection into HFs at various murine hair cycle stages. The local injection of rhDecorin (100 μg/ml) into the hypodermis of depilated C57BL/6 mice at anagen delayed catagen progression. In contrast, rhDecorin injection during the telogen phase caused the premature onset of anagen, as demonstrated by assessment of the following parameters: (1) hair shaft length, (2) follicular bulbar diameter, (3) hair follicle cycling score, and (4) follicular phase percentage. Taken together, our results suggest that decorin may modulate follicular cycling and morphogenesis. In addition, this study also provides insight into the molecular control mechanisms governing hair follicular epithelial-mesenchymal interactions.This article is protected by copyright. All rights reserved.
Article
Hair follicle stem cells and dermal papilla cells play essential roles in the cyclical hair regeneration process. However, compared with the recent progress of follicular stem cell research, detailed analysis of dermal papilla cells is virtually unknown. We have focused on a large chondroitin sulfate proteoglycan molecule, versican, and prove its pivotal role in hair follicle induction both in vitro and in vivo. First, we examined versican expression with hair cycling by in situ hybridization (mRNA) and immunohistochemistry (protein). Results clearly showed specific versican expression in anagen onset of dermal papilla cells implying a function role of versican in hair induction. We then generated transgenic lines with LacZ or green fluorescent protein reporter genes under a versican regulatory element (promoter) control, and confirmed dermal papilla-specific activation of the reporter. These transgenic lines were utilized to isolate the dermal papilla cell population by means of a fluorescent activated cell sorter.
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We studied the influence of hydrocortisone (HC) on hyaluronan (HA) metabolism in explants of human skin, a model retaining normal three-dimensional architecture of dermal connective tissue and dynamic growth and stratification of epidermal keratinocytes. The synthesis of hyaluronan and proteoglycans (PGs), and DNA, were determined with 3H-glucosamine and 3H-thymidine labelings, respectively. The total content and histological distribution of hyaluronan was studied utilizing a biotinylated aggrecan-link protein complex. A low concentration of HC (10−9 M) stimulated the incorporation of 3H-glucosamine into hyaluronan in epidermis by 23% and reduced the disappearance rate of hyaluronan by 25% in chase experiments, resulting in a 74% increase in total hyaluronan (per epidermal dry weight) after a 5-day culture in 10−9 M HC. On the other hand, a high concentration of HC (10−5 M) reduced both synthesis (-42%) and degradation (-46%) of epidermal hyaluronan during 24 h labeling and chase periods. The cumulative effect of a 5-day treatment was a 24% decrease of total epidermal hyaluronan. The high dose (10−5 M) also reduced keratinocyte DNA synthesis and epidermal thickness. In dermis, only the high (10−5 M) concentration of HC was effective, inhibiting the incorporation of 3H-glucosamine into hyaluronan by 28%. No significant influences on total hyaluronan content or the disappearance rate of hyaluronan in dermal tissue was found. All HC concentrations lacked significant effects on newly synthesized PGs in epidermal and dermal tissues, but reduced the labeled PGs diffusing into culture medium. A low physiological concentration of HC thus maintains active synthesis and high concentration of hyaluronan in epidermal tissue, while high pharmacological doses of HC slows hyaluronan turnover and reduces its content in epidermis, an effect correlated with enhanced terminal differentiation, reduced proliferation rate and reduced number of vital keratinocyte layers.
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Interest in the hair follicle (HF) has recently increased, yet the detailed mechanisms of HF function and immune privilege (IP) have not yet been elucidated. This review discusses the critical points of immunobiology and hormonal aspects of HFs. The HF is a unique mini-organ because it has its own immune system and hormonal milieu. In addition, the HF immune and hormonal systems may greatly affect skin immunobiology. Therefore, knowledge of HF immunobiology and hormonal aspects will lead to a better understanding of skin biology. The HF has a unique hair cycle (anagen, catagen and telogen) and contains stem cells in the bulge area. The HF is closely related to sebaceous glands and the nervous system. This article reviews the interaction between the endocrine/immune system and HFs, including the pathogenesis of alopecia areata associated with stress.