Hormones and Hair Growth: Variations in Androgen Receptor Content of Dermal papilla Cells Cultured from Human and Red Deer (Cervus Elaphus) Hair Follicles.

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

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Platelet factor 4 inhibits human hair follicle growth and promotes androgen receptor expression in human dermal papilla cells

PeerJ ◽

10.7717/peerj.9867 ◽

2020 ◽

Vol 8 ◽

pp. e9867

Author(s):

Ke Sha ◽

Mengting Chen ◽

Fangfen Liu ◽

San Xu ◽

Ben Wang ◽

...

Keyword(s):

Androgen Receptor ◽

Hair Follicle ◽

Human Hair ◽

Hair Growth ◽

Dermal Papilla ◽

Follicle Growth ◽

Human Hair Follicle ◽

Dermal Papilla Cells ◽

Platelet Factor ◽

Hair Follicle Growth

Platelet-rich plasma (PRP) has been reported recently as a potential therapeutic approach for alopecia, such as androgenetic alopecia, but the exact mechanisms and effects of specific components of this recipe remain largely unknown. In this study, we identified that platelet factor 4 (PF4), a component of PRP, significantly suppressed human hair follicle growth and restrained the proliferation of human dermal papilla cells (hDPCs). Furthermore, our results showed that PF4 upregulated androgen receptor (AR) in human dermal papilla cells in vitro and via hair follicle organ culture. Among the hair growth-promoting and DP-signature genes investigated, PF4 decreased the expression of Wnt5a, Wnt10b, LEF1, HEY1 and IGF-1, and increased DKK1 expression, but did not affect BMP2 and BMP4 expression. Collectively, Our data demonstrate that PF4 suppresses human hair follicle growth possibly via upregulating androgen receptor signaling and modulating hair growth-associated genes, which provides thought-provoking insights into the application and optimization of PRP in treating hair loss.

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Androgen receptors are only present in mesenchyme-derived dermal papilla cells of red deer (Cervus elaphus) neck follicles when raised androgens induce a mane in the breeding season

Journal of Endocrinology ◽

10.1677/joe.0.1680401 ◽

2001 ◽

Vol 168 (3) ◽

pp. 401-408 ◽

Cited By ~ 18

Author(s):

MJ Thornton ◽

NA Hibberts ◽

T Street ◽

BR Brinklow ◽

AS Loudon ◽

...

Keyword(s):

Breeding Season ◽

Cervus Elaphus ◽

Red Deer ◽

Androgen Receptors ◽

Dermal Papilla ◽

Nuclear Staining ◽

Dermal Papilla Cells ◽

High Affinity ◽

Androgen Binding ◽

Androgen Levels

Red deer stags produce an androgen-dependent mane of long hairs only in the breeding season; in the non-breeding season, when circulating androgen levels are low, the neck hair resembles the rest of the coat. This study was designed to determine whether androgen receptors are present in deer follicles throughout the year or only in the mane (neck) follicles when circulating testosterone levels are high in the breeding season. Although androgens regulate much human hair growth the mechanisms are not well understood; they are believed to act on the hair follicle epithelium via the mesenchyme-derived dermal papilla. The location of androgen receptors in the follicle was investigated by immunohistochemistry and androgen binding was measured biochemically in cultured dermal papilla cells derived from mane and flank follicles during the breeding season and from neck follicles during the non-breeding season. Immunohistochemistry of frozen skin sections using a polyclonal antibody to the androgen receptor localised nuclear staining only in the dermal papilla cells of mane follicles. Saturation analysis assays of 14 primary dermal papilla cell lines using [(3)H]-mibolerone demonstrated high-affinity, low-capacity androgen receptors were present only in mane (breeding season neck) cells; competition studies with other steroids confirmed the specificity of the receptors. Androgen receptors were not detectable in cells from either the breeding season flank nor the non-breeding season neck follicles. The unusual biological model offered by red deer of androgen-dependent hair being produced on the neck in the breeding, but not the non-breeding season, has allowed confirmation that androgen receptors are required in follicle dermal papilla cells for an androgen response; this concurs with previous human studies. In addition, the absence of receptors in the non-breeding season follicles demonstrates that receptors are not expressed unless the follicle is responding to androgens. Androgen receptors may be induced in mane follicles by seasonal changes in circulating hormone(s).

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Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4395638 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Jae Young Yu ◽

Biki Gupta ◽

Hyoung Geun Park ◽

Miwon Son ◽

Joon-Ho Jun ◽

...

Keyword(s):

Clinical Study ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

Herbal Extract ◽

Control Group ◽

Dependent Manner ◽

Ki 67 ◽

Dermal Papilla Cells

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner (p<0.05), and 100 ppm of DA-5512 and 1 μM minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group (p<0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p<0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD (p<0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

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

Journal of Endocrinology ◽

10.1677/joe-07-0522 ◽

2008 ◽

Vol 197 (1) ◽

pp. 11-23 ◽

Cited By ~ 29

Author(s):

Valerie A Randall ◽

Tracey J Jenner ◽

Nigel A Hibberts ◽

Isabel O De Oliveira ◽

Tayyebeh Vafaee

Keyword(s):

Stem Cell ◽

Stem Cell Factor ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

Androgenetic Alopecia ◽

Hair Colour ◽

Outer Root Sheath ◽

Dermal Papilla Cells ◽

Factor C

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.

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Kojyl Cinnamate Ester Derivatives Increase Adiponectin Expression and Stimulate Adiponectin-Induced Hair Growth Factors in Human Dermal Papilla Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20081859 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1859 ◽

Cited By ~ 6

Author(s):

Phil June Park ◽

Eun-Gyung Cho

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Mrna Expression ◽

Hair Growth ◽

Subcutaneous Fat ◽

Dermal Papilla ◽

Hair Follicles ◽

Dermal Papilla Cells ◽

Glucose Levels ◽

Endothelial Growth Factor

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.

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