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The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth

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Abstract

It is known that baldness caused by androgenetic alopecia is involved with androgen and the androgen receptor. Furthermore, it has been reported that testosterone secretion follows a circadian rhythm. Therefore, we hypothesized that a relationship exists between androgen-induced alopecia and biological rhythm. The mammalian circadian rhythm is controlled by several clock genes. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), one of the clock genes, is a transcription factor that plays central roles in the regulation of circadian rhythms. In this study, we investigated the influence of BMAL1 on hair follicle functions and hair growth. Mice deficient in BMAL1 expression exhibited a delay in hair regrowth after shaving. In hair follicles of mouse vibrissa, expression of Bmal1 and other clock genes was found to be rhythmic. Knockdown of BMAL1 in human follicle dermal papilla cells resulted in modulation of expression of several hair growth-related genes. Therefore, we concluded that expression of clock genes in hair follicles is linked to the circadian rhythm and that BMAL1 can regulate hair growth.

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References

  1. Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009–1017

    Article  PubMed  CAS  Google Scholar 

  2. Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96:271–290

    Article  PubMed  CAS  Google Scholar 

  3. Geyfman M, Kumar V, Liu Q, Ruiz R, Gordon W, Espitia F, Cam E, Millar SE, Smyth P, Ihler A, Takahashi JS, Andersen B (2012) Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci USA 109:11758–11763

    Article  PubMed  CAS  Google Scholar 

  4. Hayes LD, Bickerstaff GF, Baker JS (2010) Interactions of cortisol, testosterone, and resistance training: influence of circadian rhythms. Chronobiol Int 27:675–705

    Article  PubMed  CAS  Google Scholar 

  5. Hirsso P, Laakso M, Matilainen V, Hiltunen L, Rajala U, Jokelainen J, Keinänen-Kiukaanniemi S (2006) Association of insulin resistance linked diseases and hair loss in elderly men. Finnish population-based study. Cent Eur J Public Health 14:78–81

    PubMed  Google Scholar 

  6. Hoffmann R (2003) Steroidogenic isoenzymes in human hair and their potential role in androgenetic alopecia. Dermatology 206:85–95

    Article  PubMed  CAS  Google Scholar 

  7. Inui S, Itami S (2011) Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla. J Dermatol Sci 61:1–6

    Article  PubMed  CAS  Google Scholar 

  8. Inui S, Itami S (2013) Androgen actions on the human hair follicle: perspectives. Exp Dermatol 22:168–171

    Article  PubMed  CAS  Google Scholar 

  9. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20:1868–1873

    Article  PubMed  CAS  Google Scholar 

  10. Koyama T, Kobayashi K, Wakisaka N, Hirayama N, Konishi S, Hama T, Takeda K, Nakamizo Y, Kawakami M (2013) Eleven pairs of Japanese male twins suggest the role of epigenetic differences in androgenetic alopecia. Eur J Dermatol 23:113–115

    PubMed  Google Scholar 

  11. Lin KK, Kumar V, Geyfman M, Chudova D, Ihler AT, Smyth P, Paus R, Takahashi JS, Andersen B (2009) Circadian clock genes contribute to the regulation of hair follicle cycling. PLoS Genet 5:e1000573

    Article  PubMed  Google Scholar 

  12. Lowrey PL, Takahashi JS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5:407–441

    Article  PubMed  CAS  Google Scholar 

  13. Mermall H, Sothern RB, Kanabrocki EL, Quadri SF, Bremner FW, Nemchausky BA, Scheving LE (1995) Temporal (circadian) and functional relationship between prostate-specific antigen and testosterone in healthy men. Urology 46:45–53

    Article  PubMed  CAS  Google Scholar 

  14. Mora-Rodríguez R, García Pallarés J, López-Samanes Á, Ortega JF, Fernández-Elías VE (2012) Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS ONE 7:e33807

    Article  PubMed  Google Scholar 

  15. Paus R, Cotsarelis G (1999) The biology of hair follicles. N Engl J Med 341:491–497

    Article  PubMed  CAS  Google Scholar 

  16. Randall VA, Hibberts NA, Thornton MJ, Hamada K, Merrick AE, Kato S, Jenner TJ, De Oliveira I, Messenger AG (2000) The hair follicle: a paradoxical androgen target organ. Horm Res 54:243–250

    Article  PubMed  CAS  Google Scholar 

  17. Randall VA (2007) Hormonal regulation of hair follicles exhibits a biological paradox. Semin Cell Dev Biol 18:274–285

    Article  PubMed  CAS  Google Scholar 

  18. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    Article  PubMed  CAS  Google Scholar 

  19. Rogers NE, Avram MR (2008) Medical treatments for male and female pattern hair loss. J Am Acad Dermatol 59:547–566

    Article  PubMed  Google Scholar 

  20. Severi G, Sinclair R, Hopper JL, English DR, McCredie MR, Boyle P, Giles GG (2003) Androgenetic alopecia in men aged 40–69 years: prevalence and risk factors. Br J Dermatol 149:1207–1213

    Google Scholar 

  21. Shimba S, Ishii N, Ohta Y, Ohno T, Watabe Y, Hayashi M, Wada T, Aoyagi T, Tezuka M (2005) Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci USA 102:12071–12076

    Article  PubMed  CAS  Google Scholar 

  22. Shimba S, Ogawa T, Hitosugi S, Ichihashi Y, Nakadaira Y, Kobayashi M, Tezuka M, Kosuge Y, Ishige K, Ito Y, Komiyama K, Okamatsu-Ogura Y, Kimura K, Saito M (2011) Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation. PLoS ONE 6:e25231

    Article  PubMed  CAS  Google Scholar 

  23. Stenn KS, Paus R (2001) Controls of hair follicle cycling. Physiol Rev 81:449–494

    PubMed  CAS  Google Scholar 

  24. Su LH, Chen TH (2007) Association of androgenetic alopecia with smoking and its prevalence among Asian men: a community-based survey. Arch Dermatol 143:1401–1406

    Article  PubMed  Google Scholar 

  25. Takarada T, Kodama A, Hotta S, Mieda M, Shimba S, Hinoi E, Yoneda Y (2012) Clock genes influence gene expression in growth plate and endochondral ossification in mice. J Biol Chem 287:36081–36095

    Article  PubMed  CAS  Google Scholar 

  26. Trüeb RM (2002) Molecular mechanisms of androgenetic alopecia. Exp Gerontol 37:981–990

    Article  PubMed  Google Scholar 

  27. Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science 264:719–725

    Article  PubMed  CAS  Google Scholar 

  28. Young MW, Kay SA (2001) Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2:702–715

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Stem Cell Therapy (Endowed Chair by ANGFA Co.), St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan

    Yuichi Watabe, Ai Watabe & Hajime Inoue

  2. Department of Plastic and Reconstructive Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan

    Miyuki Tomioka, Masaki Aihara & Hajime Inoue

  3. Department of Heath Science, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan

    Shigeki Shimba

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  1. Yuichi Watabe
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  2. Miyuki Tomioka
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  3. Ai Watabe
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Correspondence to Yuichi Watabe.

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Watabe, Y., Tomioka, M., Watabe, A. et al. The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth. Arch Dermatol Res 305, 755–761 (2013). https://doi.org/10.1007/s00403-013-1403-0

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  • DOI: https://doi.org/10.1007/s00403-013-1403-0

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