Androgen Receptors in Dermal Papilla Cells of Scalp Hair Follicles in Male Pattern Baldness

Hodgins, Malcolm B.; Choudhry, R.; Parker, Gillian A.; Oliver, R. F.; Jahoda, Colin A.B.; Withers, Anne P.; Brinkmann, Albert O.; Boersma, W.J.A.; Lammers, Karen M.; Wong, Teresa; Wawrzyniak, C.J.; Warren, Raphael

doi:10.1111/j.1749-6632.1991.tb24413.x

Cited by 15 publications

(9 citation statements)

References 2 publications

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“…Additionally, ROS are a key inducer of retinoblastoma-mediated senescence (25). As nHPDCs also express androgens at a high level (26), the present study investigated whether 1 mM DHT induced ROS in these cells.…”

Section: Dht Induces Cell Death and Cell Cycle Arrest In Nhdpcsmentioning

confidence: 98%

Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Lee¹,

Jun²,

Lim³

et al. 2012

Molecular Medicine Reports

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Clinical evidence has demonstrated that the accumulation of 5α-dihydrotestosterone (DHT) in dermal papilla cells (DPCs) is implicated in androgenetic alopecia. Whether this accumulation in DHT may have direct cellular effects leading to androgenetic alopecia remains to be elucidated. The present study aimed to determine whether DHT affects cell growth, cell cycle arrest, cell death, senescence and the induction of reactive oxygen species (ROS), and whether these effects are mediated by microRNA (miRNA)-dependent mechanisms. The cell viability and cell cycle were determined, levels of ROS were examined and senescence-associated β-galactosidase assays were performed in normal human DPCs (nHDPCs). Furthermore, miRNA expression profiling was performed using an miRNA microarray to determine whether changes in the expression levels of miRNA were associated with the cellular effects of DHT. The results revealed that DHT decreased cell growth by inducing cell death and G2 cell cycle arrest, and by increasing the production of ROS and senescence in the nHDPCs. In addition, 55 miRNAs were upregulated and 6 miRNAs were downregulated in the DHT-treated nHDPCs. Bioinformatic analysis demonstrated that the putative target genes of these upregulated and downregulated miRNAs were involved in cell growth, cell cycle arrest, cell death, senescence and the production of ROS. Specifically, the target genes of five highly upregulated and downregulated miRNAs were identified and were associated with the aforementioned effects of DHT. These results demonstrated that the expression of miRNA was altered in the DHT-treated nHDPCs and suggest the potential mechanisms of DHT-induced cell growth repression, cell cycle arrest, cell death, senescence and induction of ROS.

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Section: Dht Induces Cell Death and Cell Cycle Arrest In Nhdpcsmentioning

confidence: 98%

Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Lee¹,

Jun²,

Lim³

et al. 2012

Molecular Medicine Reports

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show abstract

“…DPCs, located at the base of the hair follicle, are essential to the hair growth process. DPCs have the most consistent AR expression among all compartments of the hair follicle (Hodgins et al, 1991) and thus are the postulated sites of androgen response, where AR activation by androgens affects gene expression regulating hair growth and cycle (Itami et al, 1994;Kitagawa et al, 2009). To date, only a macroarraybased comparative study interrogating 1,185 genes has been conducted on primary DPCs from balding and non-balding scalps (Midorikawa et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Chew

Tan

Bahta

et al. 2016

Journal of Investigative Dermatology

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Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date, but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPCs) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPCs in hair-related studies often lack dermal papilla characteristics. In contrast, immortalized DPCs have high resemblance to intact dermal papilla. We derived immortalized human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retained high proportions of dermal papilla signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 (twist family basic helix-loop-helix transcription factor 1) and SSPN (sarcospan) to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularization around the hair follicle may contribute to the development of AGA.

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“…AR, a nuclear receptor, is mainly expressed in dermal papilla cells (DPCs) of the human hair follicle 16 – 18 . When DHT enters the cell, the AR protein forms a dimer with it in the cytosol, translocates to the nucleus and acts as a transcription factor to promote the expression of inhibitory proteins of hair growth (such as TGF-β and DKK-1) 8 , 19 – 23 .…”

Section: Introductionmentioning

confidence: 99%

Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia

Yun¹,

Lee²,

Goh³

et al. 2022

Sci Rep

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Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. Dihydrotestosterone (DHT) and androgen receptor (AR) levels are increased in patients with AGA, and DHT-AR signaling correlates strongly with AGA pathogenesis. In this study, treatment with self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticle-type siRNA selectively suppressed AR expression in vitro. Clinical studies with application of SAMiRNA to the scalp and massaging to deliver it to the hair follicle confirmed its efficacy in AGA. For identification of a potent SAMiRNA for AR silencing, 547 SAMiRNA candidates were synthesized and screened. SAMiRNA-AR68 (AR68) was the most potent and could be efficiently delivered to human follicle dermal papilla cells (HFDPCs) and hair follicles, and this treatment decreased the AR mRNA and protein levels. We confirmed that 10 µM AR68 elicits no innate immune response in human PBMCs and no cytotoxicity up to 20 µM with HFDP and HaCaT cells. Clinical studies were performed in a randomized and double-blind manner with two different doses and frequencies. In the low-dose (0.5 mg/ml) clinical study, AR68 was applied three times per week for 24 weeks, and through quantitative analysis using a phototrichogram, we confirmed increases in total hair counts. In the high-dose (5 mg/ml) clinical study, AR68 was given once per week for 24 weeks and showed 83% efficacy in increasing hair counts compared with finasteride. No side effects were observed. Therefore, SAMiRNA targeting AR mRNA is a potential novel topical treatment for AGA.

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Androgen Receptors in Dermal Papilla Cells of Scalp Hair Follicles in Male Pattern Baldness

Cited by 15 publications

References 2 publications

Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia

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