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| ABSTRACT |
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| Year : 2011 | Volume
: 3
| Issue : 3 | Page : 6-7 |
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Session A: Androgenetic Alopecia – Part I
| Date of Web Publication | 16-Jun-2011 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
. Session A: Androgenetic Alopecia – Part I. Int J Trichol 2011;3, Suppl S1:6-7 |
Oxidative stress plays a direct role in mediating DHT-stimulated TGF-β secretion by dermal papilla cells
Jamie Upton*, Adiam Bahta, Nilofer Farjo 1 , Bessam Farjo 1 , Mike Philpott
Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK; 1 Farjo Medical Centre, Manchester, UK.
*E-mail: [email protected]
We investigated the effects of oxygen on secretion of TGF-β in response to dihydrotestosterone (DHT). Dermal papilla cells (DPCs) from frontal hair follicles were grown as explant cultures from biopsies donated by patients undergoing hair transplant. DPCs were split between normal tissue culture conditions of 5% CO 2 20% O 2 or low oxygen conditions of 5% CO 2 2% O 2. We have previously shown that under 20% O 2, frontal DPCs exhibit reduced growth rate and higher levels of reactive oxygen species (ROS) compared with those grown under 2% O 2. We show that the ROS state of DPCs correlates with the effects of DHT on TGF-β secretion. We found that under 20% O2 DHT stimulated TGF-β secretion, as previously published (Inui et al. 2002), whereas 2% O 2 negates and in some cases may even reverse DHT-stimulated TGF-β secretion by DPCs. Moreover, by using hydrogen peroxide to chemically induce oxidative stress, we observed an increase in the amounts of TGF-β secreted by the DPCs. These data suggest that oxidative stress may exacerbate the onset of androgenic alopecia by affecting TGF-β secretion, a known inhibitor of hair follicle growth and inducer of catagen.
The first genome-wide survey of copy number variants in androgenetic alopecia suggests an involvement of a mircoduplication in 22q11.23
Stefanie Heilmann 1,2 *, Lutz Priebe 1,2 , Margrieta Alblas 1,2 , Christian Meesters 3,4 , Christine Herold 3 , Sibylle Eigelshoven 5 , Sandra Hanneken 5 , Ulla Roggenbuck 6 , Susanne Moebus 6 , Dale Nyholt 7 , Nick Martin 8 , Roland Kruse 9 , Axel M. Hillmer 10 , Tim Becker 3,4 , Markus M. Nöthen 1,2 , Felix F. Brockschmidt 1,2
1 Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany; 2 Institute of Human Genetics, University of Bonn, Bonn, Germany; 3 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; 4 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany; 5 Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany; 6 Institute for Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Essen, Germany; 7 Neurogenetics Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia; 8 Genetic Epidemiology, Queensland Institute of Medical Research, Herston, Queensland, Australia; 9 Gemeinschaftspraxis für Dermatologie, Paderborn, Germany; 10 Genome Technology and Biology Group, Genome Institute of Singapore, Singapore.
*E-mail: [email protected]
Androgenetic alopecia (AGA, male-pattern baldness) is the most common form of hair loss in humans and is characterized by a progressive loss of hair from the scalp. The pathogenesis of AGA is driven by androgens based on a genetic predisposition as the major prerequisite of the phenotype. Studies aiming at identifying the causative genetic factors at the molecular level have identified single nucleotide polymorphisms (SNPs) at the X-chromosomal androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus and within an approximately 300kb intergenic region on chromosome (chr) 20p11 to be strongly associated with AGA. Structural genomic variations, such as copy number variations (CNVs), have been recognized as another important source of genetic variability. We therefore systematically screened for a potential involvement of CNVs in the development of AGA using genome-wide SNP-array data of a well characterized German case-control sample comprising 432 unrelated AGA-affected individuals and 547 controls. We identified a total of six autosomal CNV-regions that showed nominal significant association with AGA: one rare microduplication in chr6q26, two common microdeletions in chr4q28.3 and chr14q11.2 and three common microduplications in chr11q25, chr12q13.13 and chr22q11.23. Five of the six regions could reliably be confirmed by real-time quantitative PCR. Replication analysis of the confirmed CNVs in two independent samples revealed a genome-wide significant association of a 236.4kb microduplication in chr22q11.23 that includes three RefSeq genes (IGLL3P, LRP5L, CRYBB2P1). None of these genes has previously been reported in association with hair phenotypes. Our present study thus holds evidence for an involvement of CNVs in AGA-aetiology.
Clinical experience of androgenetic alopecia in 11 pairs of identical twin males
Taro Koyama*, Kazuhiro Kobayashi, Nagaoki Wakisaka, Nobuo Hirayama, Sawako Konishi, Satoko Hamanaka, Yasutaka Fukuda, Masayuki Taguchi, Nobutaka Usui, Eriko Nakano, Ryo Nagasaka, Yoshihiro Yasuda, Tetsunori Boku, Takanori Hama, Yoshio Nakamizo, Nobuyuki Shioya, Katsuyuki Takeda, Masaya Kawakami
NPO Future Medical Laboratory, Tokyo, Japan.
*E-mail: [email protected]
Androgenetic alopecia (AGA) is thought to be influenced by environmental factors as well as genetic factors. We compared hair volume differences in identical twins to see the effect of environmental factors on AGA. 11 pairs of Japanese identical twins (the age of 20-40, initial symptom of II-vertex to V evaluated by modified Hamilton-Norwood classification) participated in the study. Patients using minoxidil or finasteride before the study were excluded. The difference in hair volume in each pair was evaluated with standardized clinical photographs using a 4 staging scale (significantly, moderately, slightly different and no difference). Nine of 11 pairs received minoxidil and finasteride for 1 year, and hair volume differences in each pair were evaluated again at 1 year after initial consultation. Information on smoking and alcohol use was collected and evaluated in association to hair volume differences. Five of the 11 pairs showed baseline differences in hair volume (significantly or moderately different). After subjecting these five pairs to medications, 4 of 5 showed differences again at 1 year after treatment. Among the 6 pairs who showed no difference at initial consultation, 4 of them received medication for 1 year. These 4 pairs showed no difference again at 1 year after treatment. Alcohol and smoking showed no association to hair volume differences 5 of 11 pairs of identical twins showed differences in hair volume and treatment efficacy. It was demonstrated that environmental factors might play an important role in hair loss progression and treatment efficacy in AGA.
Bimatoprost, a prostamide F2α analogue used for glaucoma, stimulates scalp hair follicle growth via receptors in the dermal papilla; is this a new approach for alopecia?
Karzan G. Khidhir*, Nilofer P. Farjo 1 , Bessam K. Farjo 1 , David F. Woodward 2 , Steven M. Picksley, Valerie A. Randall
Centre for Skin Sciences, University of Bradford, Bradford, United Kingdom; 1 Farjo Medical Centre, Manchester, United Kingdom; and 2 Allergan Inc, Irvine, CA, USA.
*E-mail: [email protected]
Bimatoprost, a prostamide F2α analogue treatment for glaucoma (ocular hypertension), stimulates eyelash growth as a side effect. As Latisse, it recently gained FDA approval as eyelash hypotrichosis therapy. How bimatoprost works is unknown; possibilities include direct action on hair follicles or stimulating follicular blood flow. To determine whether scalp hair follicles can respond to bimatoprost, since follicular responses often vary with body site, and to check whether any effect is through follicular receptors, scalp follicles were cultured with bimatoprost ± an antagonist and the location of the prostaglandin and prostamide F2α receptors (FP and FP-variants) investigated. Scalp hair follicles were individually micro-dissected and cultured for 9 days with daily examination, photography and measurement or micro-dissected to component parts and pooled for each person for RT-PCR using specific primers. Bimatoprost at 10 nM, 100 nM and 1μM significantly stimulated the hair follicle growth rate, percentage of anagen follicles, and overall amount of hair produced in a dose-responsive manner (n=10; P<0.05-0.01); the antagonist, AGN211336, blocked this. RT-PCR identified FP, altFP4, altFP1 gene expression only in dermal papillae and bulbar dermal sheath of follicles from 5 individuals. Therefore, isolated human scalp hair follicles respond biologically to bimatoprost in organ culture and express the genes for FP and prostamide F2α receptor. Bimatoprost presumably acts directly on receptors within the follicular dermal papilla, altering paracrine factor production which regulates keratinocytes etc. to stimulate hair growth. Bimatoprost and related drugs appear to offer an exciting, novel approach for the treatment of alopecia; this merits clinical investigation.
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