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Androgenetic alopecia: a review

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Abstract

Purpose

Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia.

Methods

Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016.

Results

The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome AR⁄EDA2R locus and the chromosome 20p11 locus.

Conclusions

Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.

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References

  1. J.B. Hamilton, Patterned loss of hair in man; types and incidence. Ann. N. Y. Acad. Sci. 53, 708–728 (1951)

    CAS  PubMed  Google Scholar 

  2. L. Yip, S. Zaloumis, D. Irwin, G. Severi, J. Hopper, G. Giles, S. Harrap, R. Sinclair, J. Ellis, Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. Br. J. Dermatol. 161, 289–294 (2009)

    CAS  PubMed  Google Scholar 

  3. G. Severi, R. Sinclair, J.L. Hopper, D.R. English, M.R.E. McCredie, P. Boyle, G.G. Giles, Androgenetic alopecia in men aged 40–69 years: prevalence and risk factors. Br. J. Dermatol. 149, 1207–1213 (2003)

    CAS  PubMed  Google Scholar 

  4. N. Otberg, A.M. Finner, J. Shapiro, Androgenetic alopecia. Endocrinol. Metab. Clin. N. Am. 36, 379–398 (2007)

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. C. Pierard-Franchimont, G.E. Pierard, Teloptosis, a turning point in hair shedding biorhythms. Dermatology 203, 115–117 (2001)

    CAS  PubMed  Google Scholar 

  7. W.C. Chumlea, T. Rhodes, C.J. Girman, A. Johnson-Levonas, F.R.W. Lilly, R. Wu, S.S. Guo, Family history and risk of hair loss. Dermatology 209, 33–39 (2004)

    PubMed  Google Scholar 

  8. D. Osborn, Inheritance of baldness. Various patterns due to heredity and sometimes present at birth—a sex-limited character-dominant in man–women not bald unless they inherit tendency from both parents. J. Hered. 7, 347–355 (1916)

    Google Scholar 

  9. W. Kuster, R. Happle, The inheritance of common baldness: two B or not two B ? J. Am. Acad. Dermatol. 11, 921–926 (1984)

    CAS  PubMed  Google Scholar 

  10. E. Levy-Nissenbaum, M. Bar-Natan, M. Frydman, E. Pras, Confirmation of the association between male pattern baldness and the androgen receptor gene. Eur. J. Dermatol. 15, 339–340 (2005)

    CAS  PubMed  Google Scholar 

  11. C.C. Zouboulis, K. Degitz, Androgen action on human skin—from basic research to clinical significance. Exp. Dermatol. 13, 5–10 (2004)

    CAS  PubMed  Google Scholar 

  12. K.S. Stenn, R. Paus, T. Dutton, B. Sarba, Glucocorticoid effect on hair growth initiation: a reconsideration. Skin Pharmacol. 6, 125–134 (1993)

    CAS  PubMed  Google Scholar 

  13. D. Deplewski, R.L. Rosenfield, Role of hormones in pilosebaceous unit development. Endocr. Rev. 21, 363–392 (2000)

    CAS  PubMed  Google Scholar 

  14. C. Roh, Q. Tao, S. Lyle, Dermal papilla-induced hair differentiation of adult epithelial stem cells from human skin. Physiol. Genom. 19, 207–217 (2004)

    CAS  Google Scholar 

  15. C. Blanpain, W.E. Lowry, A. Geoghegan, L. Polak, E. Fuchs, Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118, 635–648 (2004)

    CAS  PubMed  Google Scholar 

  16. V. Randall, in Hair and its Disorders: Biology, Pathology and Management, ed. By F. Camacho, V.A. Randall, P.V. The biology of androgenetic alopecia (Martin Dunitz, London, 2000), pp. 123–136

    Google Scholar 

  17. A.J. Reynolds, R.F. Oliver, C.A. Jahoda, Dermal cell populations show variable competence in epidermal cell support: stimulatory effects of hair papilla cells. J. Cell Sci. 98(Pt 1), 75–83 (1991)

    PubMed  Google Scholar 

  18. N.A. Hibberts, A.E. Howell, V.A. Randall, Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J. Endocrinol. 156, 59–65 (1998)

    CAS  PubMed  Google Scholar 

  19. V.A. Botchkarev, J. Kishimoto, Molecular control of epithelial-mesenchymal interactions during hair follicle cycling. in Journal of Investigative Dermatology Symposium Proceedings. pp 46–55 (2003)

    CAS  Google Scholar 

  20. V.A. Randall, M.J. Thornton, A.G. Messenger, Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp. J. Endocrinol. 133, 141–147 (1992)

    CAS  PubMed  Google Scholar 

  21. S. Itami, S. Kurata, S. Takayasu, Androgen induction of follicular epithelial cell growth is mediated via insulin-like growth factor-I from dermal papilla cells. Biochem. Biophys. Res. Commun. 212, 988–994 (1995)

    CAS  PubMed  Google Scholar 

  22. S. Inui, Y. Fukuzato, T. Nakajima, K. Yoshikawa, S. Itami, Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in Androgenetic alopecia. J Investig. Dermatol. Symp. Proc. 8, 69–71 (2003)

    CAS  Google Scholar 

  23. M. Philpott, in Hair and its Disorders: Biology, Research and Management. ed. By F. Camacho, lV. Randal, V. Price. The roles of growth factors in hair follicles: investigations using cultured hair follicles (Martin Dunitz, London, 2001) pp. 103–113

    Google Scholar 

  24. R.D. Sinclair, Male androgenetic alopecia (Part II). J. Men’s Health Gend. 2, 38–44 (2005)

    Google Scholar 

  25. S. Inui, Y. Fukuzato, T. Nakajima, K. Yoshikawa, S. Itami, Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth. FASEB J. 16, 1967–1969 (2002)

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  27. T. Hibino, T. Nishiyama, Role of TGF-beta2 in the human hair cycle. J. Dermatol. Sci. 35, 9–18 (2004)

    CAS  PubMed  Google Scholar 

  28. M.H. Kwack, Y.K. Sung, E.J. Chung, S.U. Im, J.S. Ahn, M.K. Kim, J.C. Kim, Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J. Invest. Dermatol. 128, 262–269 (2008)

    CAS  PubMed  Google Scholar 

  29. M.H. Kwack, J.S. Ahn, M.K. Kim, J.C. Kim, Y.K. Sung, Dihydrotestosterone-inducible IL-6 inhibits elongation of human hair shafts by suppressing matrix cell proliferation and promotes regression of hair follicles in mice. J. Invest. Dermatol. 132, 43–49 (2012)

    CAS  PubMed  Google Scholar 

  30. V. Poor, S. Juricskay, E. Telegdy, Urinary steroids in men with male-pattern alopecia. J. Biochem. Biophys. Methods 53, 123–130 (2002)

    CAS  PubMed  Google Scholar 

  31. C.C. Zouboulis, The human skin as a hormone target and an endocrine gland. Hormones 3, 9–26 (2004)

    PubMed  Google Scholar 

  32. M. Fritsch, C.E. Orfanos, C.C. Zouboulis, Sebocytes are the key regulators of androgen homeostasis in human skin. J. Invest. Dermatol. 116, 793–800 (2001)

    CAS  PubMed  Google Scholar 

  33. L. Di Luigi, F. Romanelli, A. Lenzi, Androgenic-anabolic steroids abuse in males. J. Endocrinol. Invest. 28, 81–84 (2005)

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  35. R. Hoffmann, Enzymology of the hair follicle. Eur. J. Dermatol. 11, 296–300 (2001)

    CAS  PubMed  Google Scholar 

  36. U. Hoppe, P.-M. Holterhus, L. Wunsch, D. Jocham, T. Drechsler, S. Thiele, C. Marschke, O. Hiort, Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and the androgen receptor. J. Mol. Med. 84, 651–659 (2006)

    CAS  PubMed  Google Scholar 

  37. D. Thiboutot, P. Martin, L. Volikos, K. Gilliland, Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands. J. Invest. Dermatol. 111, 390–395 (1998)

    CAS  PubMed  Google Scholar 

  38. S. Takayasu, Metabolism and action of androgen in the skin. Int. J. Dermatol. 18, 681–692 (1979)

    CAS  PubMed  Google Scholar 

  39. D.W. Russell, D.M. Berman, J.T. Bryant, K.M. Cala, D.L. Davis, C.P. Landrum, J.S. Prihoda, R.I. Silver, A.E. Thigpen, W.C. Wigley, The molecular genetics of steroid 5 alpha-reductases. Recent Prog. Horm. Res. 49, 275–284 (1994)

    CAS  PubMed  Google Scholar 

  40. S. Nakanishi, I. Adachi, K. Takayasu. in Hair Research for the Next Millennium. ed. By D. Neste. Expression of androgen receptor, type I and type II 5a-reductase in human dermal papilla cellse (VREPB, Amsterdam, 1996) pp 333–337

    Google Scholar 

  41. Y. Asada, T. Sonoda, M. Ojiro, S. Kurata, T. Sato, T. Ezaki, S. Takayasu, 5 alpha-reductase type 2 is constitutively expressed in the dermal papilla and connective tissue sheath of the hair follicle in vivo but not during culture in vitro. J. Clin. Endocrinol. Metab. 86, 2875–2880 (2001)

    CAS  PubMed  Google Scholar 

  42. M.E. Sawaya, V.H. Price, Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J. Invest. Dermatol. 109, 296–300 (1997)

    CAS  PubMed  Google Scholar 

  43. M.E. Sawaya, N.S. Penneys, Immunohistochemical distribution of aromatase and 3B-hydroxysteroid dehydrogenase in human hair follicle and sebaceous gland. J. Cutan. Pathol. 19, 309–314 (1992)

    CAS  PubMed  Google Scholar 

  44. U. Ohnemus, M. Uenalan, J. Inzunza, J.-A. Gustafsson, R. Paus, The hair follicle as an estrogen target and source. Endocr. Rev. 27, 677–706 (2006)

    CAS  PubMed  Google Scholar 

  45. V.A. Randall, Role of 5α-reductase in health and disease, Baillière’s Clinical Endocrinology and Metabolism. 8(2), 405–431 (1994). doi:10.1016/S0950-351X(05)80259-9.

    Chapter  Google Scholar 

  46. D. Gianfrilli, S. Pierotti, R. Pofi, C. Leonardo, M. Ciccariello, F. Barbagallo, Sex steroid metabolism in benign and malignant intact prostate biopsies: individual profiling of prostate intracrinology. Biomed. Res. Int. 2014, 464869 (2014)

    PubMed  PubMed Central  Google Scholar 

  47. M.J. McPhaul, Androgen receptor mutations and androgen insensitivity. Mol. Cell. Endocrinol. 198, 61–67 (2002)

    CAS  PubMed  Google Scholar 

  48. J.D. Wilson, J.E. Griffin, D.W. Russell, Steroid 5 alpha-reductase 2 deficiency. Endocr. Rev. 14, 577–593 (1993)

    CAS  PubMed  Google Scholar 

  49. T. Liang, S. Hoyer, R. Yu, K. Soltani, A.L. Lorincz, R.A. Hiipakka, S. Liao, Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor. J. Invest. Dermatol. 100, 663–666 (1993)

    CAS  PubMed  Google Scholar 

  50. T. Tadokoro, S. Itami, K. Hosokawa, H. Terashi, S. Takayasu, Human genital melanocytes as androgen target cells. J. Invest. Dermatol. 109, 513–517 (1997)

    CAS  PubMed  Google Scholar 

  51. S. Itami, S. Kurata, T. Sonoda, S. Takayasu, Interaction between dermal papilla cells and follicular epithelial cells in vitro: effect of androgen. Br. J. Dermatol. 132, 527–532 (1995)

    CAS  PubMed  Google Scholar 

  52. S. Inui, S. Itami, H.J. Pan, C. Chang, Lack of androgen receptor transcriptional activity in human keratinocytes. J. Dermatol. Sci. 23, 87–92 (2000)

    CAS  PubMed  Google Scholar 

  53. J.E. Cobb, N.C. Wong, L.W. Yip, J. Martinick, R. Bosnich, R.D. Sinclair, J.M. Craig, R. Saffery, S.B. Harrap, J.A. Ellis, Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia. Br. J. Dermatol. 165, 210–213 (2011)

    CAS  PubMed  Google Scholar 

  54. N. Fujimoto, S. Yeh, H.Y. Kang, S. Inui, H.C. Chang, A. Mizokami, C. Chang, Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J. Biol. Chem. 274, 8316–8321 (1999)

    CAS  PubMed  Google Scholar 

  55. S. Inui, Y. Fukuzato, T. Nakajima, S. Kurata, S. Itami, Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles. J. Invest. Dermatol. 127, 2302–2306 (2007)

    CAS  PubMed  Google Scholar 

  56. S. Itami, S. Kurata, S. Takayasu, 5 Alpha-reductase activity in cultured human dermal papilla cells from beard compared with reticular dermal fibroblasts. J. Invest. Dermatol. 94, 150–152 (1990)

    CAS  PubMed  Google Scholar 

  57. S. Itami, S. Kurata, T. Sonoda, S. Takayasu, Characterization of 5 alpha-reductase in cultured human dermal papilla cells from beard and occipital scalp hair. J. Invest. Dermatol. 96, 57–60 (1991)

    CAS  PubMed  Google Scholar 

  58. P. Lee, C.-C. Zhu, N.S. Sadick, A.H. Diwan, P.S. Zhang, J.S. Liu, V.G. Prieto, Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia. J. Cutan. Pathol. 32, 567–571 (2005)

    PubMed  Google Scholar 

  59. M.E. Sawaya, A.R. Shalita, Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne. J. Cutan. Med. Surg. 3, 9–15 (1998)

    CAS  PubMed  Google Scholar 

  60. A.M. Hillmer, S. Hanneken, S. Ritzmann, T. Becker, J. Freudenberg, F.F. Brockschmidt, A. Flaquer, Y. Freudenberg-Hua, R.A. Jamra, C. Metzen, U. Heyn, N. Schweiger, R.C. Betz, B. Blaumeiser, J. Hampe, S. Schreiber, T.G. Schulze, H.C. Hennies, J. Schumacher, P. Propping, T. Ruzicka, S. Cichon, T.F. Wienker, R. Kruse, M.M. Nothen, Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am. J. Hum. Genet. 77, 140–148 (2005)

    CAS  PubMed  PubMed Central  Google Scholar 

  61. J.A. Ellis, M. Stebbing, S.B. Harrap, Polymorphism of the androgen receptor gene is associated with male pattern baldness. J. Invest. Dermatol. 116, 452–455 (2001)

    CAS  PubMed  Google Scholar 

  62. J.A. Ellis, K.J. Scurrah, J.E. Cobb, S.G. Zaloumis, A.E. Duncan, S.B. Harrap, Baldness and the androgen receptor: the AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. Hum. Genet. 121, 451–457 (2007)

    PubMed  Google Scholar 

  63. V.M. Hayes, G. Severi, Sa Eggleton, E.J.D. Padilla, M.C. Southey, R.L. Sutherland, J.L. Hopper, G.G. Giles, Short communication the E211 G > a androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. Cancer Epidemiol. 14, 993–996 (2005)

    CAS  Google Scholar 

  64. J.E. Cobb, S.J. White, S.B. Harrap, J.A. Ellis, Androgen receptor copy number variation and androgenetic alopecia: a case-control study. PLoS One 4, e5081 (2009)

    PubMed  PubMed Central  Google Scholar 

  65. D.A. Prodi, N. Pirastu, G. Maninchedda, A. Sassu, A. Picciau, M.A. Palmas, A. Mossa, I. Persico, M. Adamo, A. Angius, M. Pirastu, EDA2R is associated with androgenetic alopecia. J. Invest. Dermatol. 128, 2268–2270 (2008)

    CAS  PubMed  Google Scholar 

  66. A.M. Hillmer, J. Freudenberg, S. Myles, S. Herms, K. Tang, D.A. Hughes, F.F. Brockschmidt, Y. Ruan, M. Stoneking, M.M. Nöthen, Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness. Hum. Genet. 126, 255 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  67. F.F. Brockschmidt, A.M. Hillmer, S. Eigelshoven, S. Hanneken, S. Heilmann, S. Barth, C. Herold, T. Becker, R. Kruse, M.M. Nöthen, Fine mapping of the human AR/EDA2R locus in androgenetic alopecia. Br. J. Dermatol. 162, 899–903 (2010)

    CAS  PubMed  Google Scholar 

  68. J.A. Ellis, M. Stebbing, S.B. Harrap, Genetic analysis of male pattern baldness and the 5alpha-reductase genes. J. Invest. Dermatol. 110, 849–853 (1998)

    CAS  PubMed  Google Scholar 

  69. J.B. Richards, X. Yuan, F. Geller, D. Waterworth, V. Bataille, D. Glass, K. Song, G. Waeber, P. Vollenweider, K.K.H. Aben, L.A. Kiemeney, B. Walters, N. Soranzo, U. Thorsteinsdottir, A. Kong, T. Rafnar, P. Deloukas, P. Sulem, H. Stefansson, K. Stefansson, T.D. Spector, V. Mooser, Male-pattern baldness susceptibility locus at 20p11. Nat. Genet. 40, 1282–1284 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  70. F.F. Brockschmidt, S. Heilmann, J.A. Ellis, S. Eigelshoven, S. Hanneken, C. Herold, S. Moebus, M.A. Alblas, B. Lippke, N. Kluck, L. Priebe, F.A. Degenhardt, R.A. Jamra, C. Meesters, K.H. Jöckel, R. Erbel, S. Harrap, J. Schumacher, H. Fröhlich, R. Kruse, A.M. Hillmer, T. Becker, M.M. Nöthen, Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness. Br. J. Dermatol. 165, 1293–1302 (2011)

    CAS  PubMed  Google Scholar 

  71. A.M. Hillmer, F.F. Brockschmidt, S. Hanneken, S. Eigelshoven, M. Steffens, A. Flaquer, S. Herms, T. Becker, A.-K. Kortüm, D.R. Nyholt, Z.Z. Zhao, G.W. Montgomery, N.G. Martin, T.W. Mühleisen, M.A. Alblas, S. Moebus, K.-H. Jöckel, M. Bröcker-Preuss, R. Erbel, R. Reinartz, R.C. Betz, S. Cichon, P. Propping, M.P. Baur, T.F. Wienker, R. Kruse, M.M. Nöthen, Susceptibility variants for male-pattern baldness on chromosome 20p11. Nat. Genet. 40, 1279–1281 (2008)

    CAS  PubMed  Google Scholar 

  72. D.R. Chesire, W.B. Isaacs, Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene 21, 8453–8469 (2002)

    CAS  PubMed  Google Scholar 

  73. R. Li, F.F. Brockschmidt, A.K. Kiefer, H. Stefansson, D.R. Nyholt, K. Song, S.H. Vermeulen, S. Kanoni, D. Glass, S.E. Medland, M. Dimitriou, D. Waterworth, J.Y. Tung, F. Geller, S. Heilmann, A.M. Hillmer, V. Bataille, S. Eigelshoven, S. Hanneken, S. Moebus, C. Herold, M. den Heijer, G.W. Montgomery, P. Deloukas, N. Eriksson, A.C. Heath, T. Becker, P. Sulem, M. Mangino, P. Vollenweider, T.D. Spector, G. Dedoussis, N.G. Martin, L.A. Kiemeney, V. Mooser, K. Stefansson, D.A. Hinds, M.M. Nöthen, J.B. Richards, Six novel susceptibility loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet. 8, e1002746 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  74. T. Kitagawa, K.I. Matsuda, S. Inui, H. Takenaka, N. Katoh, S. Itami, S. Kishimoto, M. Kawata, Keratinocyte growth inhibition through the modification of wnt signaling by androgen in balding dermal papilla cells. J. Clin. Endocrinol. Metab. 94, 1288–1294 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  75. G.J. Leirõs, A.I. Attorresi, M.E. Balañá, Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia. Br. J. Dermatol. 166, 1035–1042 (2012)

    PubMed  Google Scholar 

  76. J.S. Crabtree, E.J. Kilbourne, B.J. Peano, S. Chippari, T. Kenney, C. McNally, W. Wang, H.A. Harris, R.C. Winneker, S. Nagpal, C.C. Thompson, A mouse model of androgenetic alopecia. Endocrinology 151, 2373–2380 (2010)

    CAS  PubMed  Google Scholar 

  77. F. Yang, X. Li, M. Sharma, C.Y. Sasaki, D.L. Longo, B. Lim, Z. Sun, Linking beta-catenin to androgen-signaling pathway. J. Biol. Chem. 277, 11336–11344 (2002)

    CAS  PubMed  Google Scholar 

  78. J. Kishimoto, R.E. Burgeson, B.A. Morgan, Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 14, 1181–1185 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  79. C. Lo Celso, D.M. Prowse, F.M. Watt, Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development 131, 1787–1799 (2004)

    CAS  PubMed  Google Scholar 

  80. D. Van Mater, F.T. Kolligs, A.A. Dlugosz, E.R. Fearon, Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 17, 1219–1224 (2003)

    PubMed  PubMed Central  Google Scholar 

  81. T. Andl, S.T. Reddy, T. Gaddapara, S.E. Millar, WNT signals are required for the initiation of hair follicle development. Dev. Cell 2, 643–653 (2002)

    CAS  PubMed  Google Scholar 

  82. A.A. Mills, B. Zheng, X.J. Wang, H. Vogel, D.R. Roop, A. Bradley, p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398, 708–713 (1999)

    CAS  PubMed  Google Scholar 

  83. M. Sosnova, M. Bradl, J.V. Forrester, CD34+ corneal stromal cells are bone marrow-derived and express hemopoietic stem cell markers. Stem Cells 23, 507–515 (2005)

    CAS  PubMed  Google Scholar 

  84. L.A. Garza, Y. Liu, Z. Yang, B. Alagesan, J.A. Lawson, S.M. Norberg, D.E. Loy, T. Zhao, H.B. Blatt, D.C. Stanton, L. Carrasco, G. Ahluwalia, S.M. Fischer, G.A. FitzGerald, G. Cotsarelis, Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia 4, 126ra34 (2012).

  85. S. Heilmann, D.R. Nyholt, F.F. Brockschmidt, A.M. Hillmer, C. Herold, T. Becker, N.G. Martin, M.M. Nöthen, No genetic support for a contribution of prostaglandins to the aetiology of androgenetic alopecia. Br. J. Dermatol. 169, 222–224 (2013)

    CAS  PubMed  Google Scholar 

  86. A.W. Bahta, N. Farjo, B. Farjo, M.P. Philpott, Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression. J. Invest. Dermatol. 128, 1088–1094 (2008)

    CAS  PubMed  Google Scholar 

  87. Q.M. Chen, Replicative senescence and oxidant-induced premature senescence. Beyond the control of cell cycle checkpoints. Ann. N. Y. Acad. Sci. 908, 111–125 (2000)

    CAS  PubMed  Google Scholar 

  88. J.H. Upton, R.F. Hannen, A.W. Bahta, N. Farjo, B. Farjo, M.P. Philpott, Oxidative stress–associated senescence in dermal papilla cells of men with androgenetic alopecia. J. Investig. Dermatol. Adv. Online Publ. 135, 1244–1252 (2015)

    CAS  Google Scholar 

  89. M. Bienova, R. Kucerova, M. Fiuraskova, M. Hajduch, Z. Kolar, Androgenetic alopecia and current methods of treatment. Acta. Dermatovenerol. Alp. Pannonica Adriat. 14, 5–8 (2005)

    PubMed  Google Scholar 

  90. H.S. Shin, C.H. Won, S.H. Lee, O.S. Kwon, K.H. Kim, H.C. Eun, Efficacy of 5% minoxidil versus combined 5% minoxidil and 0.01% tretinoin for male pattern hair loss: a randomized, double-blind, comparative clinical trial. Am. J. Clin. Dermatol. 8, 285–290 (2007)

    PubMed  Google Scholar 

  91. A.E. Buhl, D.J. Waldon, T.T. Kawabe, J.M. Holland, Minoxidil stimulates mouse vibrissae follicles in organ culture. J. Invest. Dermatol. 92, 315–320 (1989)

    CAS  PubMed  Google Scholar 

  92. A. Blumeyer, A. Tosti, A. Messenger, P. Reygagne, V. Del Marmol, P.I. Spuls, M. Trakatelli, A. Finner, F. Kiesewetter, R. Trüeb, B. Rzany, U. Blume-Peytavi, Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. JDDG 9, S1–S57 (2011)

    PubMed  Google Scholar 

  93. E.P. Jenkins, S. Andersson, J. Imperato-McGinley, J.D. Wilson, D.W. Russell, Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase. J. Clin. Invest. 89, 293–300 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  94. D.W. Russell, J.D. Wilson, Steroid 5 alpha-reductase: two genes/two enzymes. Annu. Rev. Biochem. 63, 25–61 (1994)

    CAS  PubMed  Google Scholar 

  95. G. Harris, B. Azzolina, W. Baginsky, G. Cimis, G.H. Rasmusson, R.L. Tolman, C.R. Raetz, K. Ellsworth, Identification and selective inhibition of an isozyme of steroid 5 alpha-reductase in human scalp. Proc. Natl Acad. Sci. USA 89, 10787–10791 (1992)

    CAS  PubMed  Google Scholar 

  96. A.E. Thigpen, R.I. Silver, J.M. Guileyardo, M.L. Casey, J.D. McConnell, D.W. Russell, Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J. Clin. Invest. 92, 903–910 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  97. E. Bayne, J. Flanagan, B. Azzolina, R. Einstein, J. Mumford, B. Avala, D. Chang, I. Thiboutot, I. Singer, G. Harris, Immunolocalization of type 2 5a-reductase in human hair follicles [abstract]. in 1997 Annual Meeting Society for Investigative Dermatology. p. 651 (1997)

  98. L. Drake, M. Hordinsky, V. Fiedler, J. Swinehart, W.P. Unger, P.C. Cotterill, D.M. Thiboutot, N. Lowe, C. Jacobson, D. Whiting, S. Stieglitz, S.J. Kraus, E.I. Griffin, D. Weiss, P. Carrington, C. Gencheff, G.W. Cole, D.M. Pariser, E.S. Epstein, W. Tanaka, A. Dallob, K. Vandormael, L. Geissler, J. Waldstreicher, The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J. Am. Acad. Dermatol. 41, 550–554 (1999)

    CAS  PubMed  Google Scholar 

  99. M. Caserini, M. Radicioni, C. Leuratti, E. Terragni, M. Iorizzo, R. Palmieri, Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia. Int. J. Clin. Pharmacol. Ther. 54, 19–27 (2016)

    CAS  PubMed  Google Scholar 

  100. M. Caserini, M. Radicioni, C. Leuratti, O. Annoni, R. Palmieri, A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels in healthy male volunteers. Int. J. Clin. Pharmacol. Ther. 52, 842–849 (2014)

    CAS  PubMed  Google Scholar 

  101. B.S. Chandrashekar, T. Nandhini, V. Vasanth, R. Sriram, S. Navale, Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride. Indian Dermatol. Online J. 6, 17–20 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Z. Hajheydari, J. Akbari, M. Saeedi, L. Shokoohi, Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia. Indian J. Dermatol. Venereol. Leprol. 75, 47–51 (2009)

    PubMed  Google Scholar 

  103. C. Tanglertsampan, Efficacy and safety of 3% minoxidil versus combined 3% minoxidil / 0.1% finasteride in male pattern hair loss: a randomized, double-blind, comparative study. J. Med. Assoc. Thail. 95, 1312–1316 (2012)

    Google Scholar 

  104. S. Khandpur, M. Suman, B.S. Reddy, Comparative efficacy of various treatment regimens for androgenetic alopecia in men. J. Dermatol. 29, 489–498 (2002)

    CAS  PubMed  Google Scholar 

  105. A.R. Diani, M.J. Mulholland, K.L. Shull, M.F. Kubicek, G.A. Johnson, H.J. Schostarez, M.N. Brunden, A.E. Buhl, Hair growth effects of oral administration of finasteride, a steroid 5α-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. J. Clin. Endocrinol. Metab. 74, 345–350 (1992)

    CAS  PubMed  Google Scholar 

  106. A. Rossi, C. Cantisani, M. Scarno, A. Trucchia, M.C. Fortuna, S. Calvieri, Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up. Dermatol. Ther. 24, 455–461 (2011)

    CAS  PubMed  Google Scholar 

  107. J.W. Overstreet, V.L. Fuh, J. Gould, S.S. Howards, M.M. Lieber, W. Hellstrom, S. Shapiro, P. Carroll, R.S. Corfman, S. Petrou, R. Lewis, P. Toth, T. Shown, J. Roy, J.P. Jarow, J. Bonilla, C.A. Jacobsen, D.Z. Wang, K.D. Kaufman, Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. J. Urol. 162, 1295–1300 (1999)

    CAS  PubMed  Google Scholar 

  108. A.M. Traish, J. Hassani, A.T. Guay, M. Zitzmann, M.L. Hansen, Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J. Sex. Med. 8, 872–884 (2011)

    CAS  PubMed  Google Scholar 

  109. M.S. Irwig, S. Kolukula. Persistent sexual side effects of finasteride for male pattern hair loss. J. Sex. Med. 8, 1747–1753 (2011)

    PubMed  Google Scholar 

  110. Y. Wu, R.R. Chhipa, H. Zhang, C. Ip, The antiandrogenic effect of finasteride against a mutant androgen receptor. Cancer Biol. Ther. 11, 902–909 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  111. D.A. Finn, S.L. Long, M.A. Tanchuck, J.C. Crabbe, Interaction of chronic ethanol exposure and finasteride: sex and strain differences. Pharmacol. Biochem. Behav. 78, 435–443 (2004)

    CAS  PubMed  Google Scholar 

  112. B. Stoffel-Wagner, Neurosteroid biosynthesis in the human brain and its clinical implications. Ann. N. Y. Acad. Sci. 1007, 64–78 (2003)

    CAS  PubMed  Google Scholar 

  113. R. Rupprecht, F. Holsboer, Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 22, 410–416 (1999)

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank Marie-Hélène Hayles for her assistance in the English translation of the manuscript. This work was supported by a grant from the Italian Ministry of Education and Research (MIUR-PRIN) and the University of Rome “La Sapienza” Faculty of Medicine.

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  1. Department of Experimental Medicine, University of Rome “La Sapienza”, Rome, Italy

    Francesca Lolli, Francesco Pallotti, Andrea Lenzi, Andrea Sansone & Francesco Lombardo

  2. Department of Internal Medicine and Medical Specialties, University of Rome “La Sapienza”, Rome, Italy

    Alfredo Rossi, Maria C. Fortuna & Gemma Caro

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  1. Francesca Lolli
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Lolli, F., Pallotti, F., Rossi, A. et al. Androgenetic alopecia: a review. Endocrine 57, 9–17 (2017). https://doi.org/10.1007/s12020-017-1280-y

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