Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla

Journal of Dermatological Science

Volumn 61, Issue 1, 2011, Pages 1-6

  Inui, Shigeki ^a   Itami, Satoshi ^a  

^a OSAKA UNIVERSITY MEDICAL SCHOOL   (Japan)

Author keywords

5 Reductase; Androgen receptor; Androgenetic alopecia; ARA55 Hic 5; DKK 1; TGF

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; DICKKOPF 1 PROTEIN; STEROID 5ALPHA REDUCTASE 1; STEROID 5ALPHA REDUCTASE 2; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2;

CELL GROWTH; EPITHELIUM CELL; HAIR FOLLICLE; HUMAN; KERATINOCYTE; MALE TYPE ALOPECIA; NONHUMAN; PARACRINE SIGNALING; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SKIN CELL; UPREGULATION;

ALOPECIA; ANDROGENS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; SIGNAL TRANSDUCTION; TESTOSTERONE;

EID: 78650677480     PISSN: 09231811     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jdermsci.2010.10.015     Document Type: Review

References (49)

1. Inui S., Nakajima T., Itami S. Scalp dermoscopy of androgenetic alopecia in Asian people. J Dermatol 2009, 36:82-85.
2. Uno H., Allegra F., Adachi K., Montagna W. Studies of common baldness of the stumptailed macaque. I. Distribution of the hair follicles. J Invest Dermatol 1967, 49:288-296.
3. Hamilton J. Male hormone is prerequisite and incitant in common baldness. Am J Anat 1942, 71:415-480.
4. Pan H.J., Wilding G., Uno H., Inui S., Goldsmith L., Messing E., et al. Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques. Endocrine 1998, 9:39-43.
5. Zouboulis C.C., Degitz K. Androgen action on human skin - from basic research to clinical significance. Exp Dermatol 2004, 13(Suppl. 4):5-10.
6. Faydaci G., Bilal E., Necmettin P., Fatih T., Asuman O., Ugur K. Baldness, benign prostate hyperplasia, prostate cancer and androgen levels. Aging Male 2008, 11:189-192.
7. Heinlein C.A., Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev 2002, 23:175-200.
8. Peterson R.E., Imperato-McGinley J., Gautier T., Sturla E. Male pseudohermaphroditism due to steroid 5-alpha-reductase deficiency. Am J Med 1977, 62:170-191.
9. Itami S., Kurata S., Sonoda T., Takayasu S. Characterization of 5 alpha-reductase in cultured human dermal papilla cells from beard and occipital scalp hair. J Invest Dermatol 1991, 96:57-60.
10. Nakanishi S., Adachi I.S., Takayasu K.S. Expression of androgen receptor, type I and type II 5a-reductase in human dermal papilla cells. Hair research for the next millennium 1996, 333-337. VREPB, Amsterdam. D. Neste (Ed.).
11. Asada Y., Sonoda T., Ojiro M., Kurata S., Sato T., Ezaki T., et al. 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 2001, 86:2875-2880.
12. Hoffmann R., Happle R. Finasteride is the main inhibitor of 5alpha-reductase activity in microdissected dermal papillae of human hair follicles. Arch Dermatol Res 1999, 291:100-103.
13. Olsen E.A., Hordinsky M., Whiting D., Stough D., Hobbs S., Ellis M.L., et al. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol 2006, 55:1014-1023.
14. Eun HC, Kwon OS, Yeon JH, Shin HS, Kim BY, Ro BI. Efficacy, safety, and tolerability of dutasteride 0.5mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. J Am Acad Dermatol; doi:10.1016/jjaad.2009.09.018.
15. Ellis J.A., Stebbing M., Harrap S.B. Genetic analysis of male pattern baldness and the 5alpha-reductase genes. J Invest Dermatol 1998, 110:849-853.
16. Ha S.J., Kim J.S., Myung J.W., Lee H.J., Kim J.W. Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia. J Dermatol Sci 2003, 31:135-141.
17. Hayes V.M., Severi G., Padilla E.J., Morris H.A., Tilley W.D., Southey M.C., et al. 5alpha-reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int J Cancer 2007, 120:776-780.
18. Evans R.M. The steroid and thyroid hormone receptor superfamily. Science 1988, 240:889-895.
19. Itami S., Kurata S., Sonoda T., Takayasu S. Mechanism of action of androgen in dermal papilla cells. Ann N Y Acad Sci 1991, 642:385-395.
20. Itami S., Kurata S., Sonoda T., Takayasu S. Interaction between dermal papilla cells and follicular epithelial cells in vitro: effect of androgen. Br J Dermatol 1995, 132:527-532.
21. Inui S., Itami S., Pan H.J., Chang C. Lack of androgen receptor transcriptional activity in human keratinocytes. J Dermatol Sci 2000, 23:87-92.
22. Hibberts N.A., Howell A.E., Randall V.A. Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol 1998, 156:59-65.
23. Hillmer A.M., Hanneken S., Ritzmann S., Becker T., Freudenberg J., Brockschmidt F.F., et al. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet 2005, 77:140-148.
24. Hayes V.M., Severi G., Eggleton S.A., Padilla E.J., Southey M.C., Sutherland R.L., et al. The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. Cancer Epidemiol Biomarkers Prev 2005, 14:993-996.
25. Thakur M.K., Paramanik V. Role of steroid hormone coregulators in health and disease. Horm Res 2009, 71:194-200.
26. Fujimoto N., Yeh S., Kang H.Y., Inui S., Chang H.C., Mizokami A., et al. Cloning and characterization of androgen receptor coactivator ARA55, in human prostate. J Biol Chem 1999, 274:8316-8321.
27. Heitzer M.D., DeFranco D.B. Mechanism of action of Hic-5/androgen receptor activator 55, a LIM domain-containing nuclear receptor coactivator. Mol Endocrinol 2006, 20:56-64.
28. Fujimoto N., Miyamoto H., Mizokami A., Harada S., Nomura M., Ueta Y., et al. Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells. Cancer Invest 2007, 25:32-37.
29. Inui S., Fukuzato Y., Nakajima T., Kurata S., Itami S. 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 2007, 127:2302-2306.
30. Yeh S., Chang C. Cloning and characterization of a specific coactivator ARA70, for the androgen receptor in human prostate cells. Proc Natl Acad Sci U S A 1996, 93:5517-5521.
31. Lee P., Zhu C.C., Sadick N.S., Diwan A.H., Zhang P.S., Liu J.S., et al. Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia. J Cutan Pathol 2005, 32:567-571.
32. Oliver R.F., Jahoda C.A. Dermal-epidermal interactions. Clin Dermatol 1988, 6:74-82.
33. Obana N., Chang C., Uno H. Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque. Endocrinology 1997, 138:356-361.
34. Itami S., Kurata S., Takayasu S. Androgen induction of follicular epithelial cell growth is mediated via insulin-like growth factor-I from dermal papilla cells. Biochem Biophys Res Commun 1995, 212:988-994.
35. Pan H.J., Uno H., Inui S., Fulmer N.O., Chang C. Roles of testosterone in the growth of keratinocytes through bald frontal dermal papilla cells. Endocrine 1999, 11:321-327.
36. Inui S., Fukuzato Y., Nakajima T., Yoshikawa K., Itami S. 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 2002, 16:1967-1969.
37. Inui S., Fukuzato Y., Nakajima T., Yoshikawa K., Itami S. Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia. J Investig Dermatol Symp Proc 2003, 8:69-71.
38. Hibino T., Nishiyama T. Role of TGF-beta2 in the human hair cycle. J Dermatol Sci 2004, 35:9-18.
39. Paus R., Foitzik K., Welker P., Bulfone-Paus S., Eichmuller S. Transforming growth factor-beta receptor type I and type II expression during murine hair follicle development and cycling. J Invest Dermatol 1997, 109:518-526.
40. Foitzik K., Lindner G., Mueller-Roever S., Maurer M., Botchkareva N., Botchkarev V., et al. Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo. FASEB J 2000, 14:752-760.
41. Soma T., Dohrmann C.E., Hibino T., Raftery L.A. Profile of transforming growth factor-beta responses during the murine hair cycle. J Invest Dermatol 2003, 121:969-975.
42. Tsuji Y., Denda S., Soma T., Raftery L., Momoi T., Hibino T. A potential suppressor of TGF-beta delays catagen progression in hair follicles. J Investig Dermatol Symp Proc 2003, 8:65-68.
43. Yoo H.G., Kim J.S., Lee S.R., Pyo H.K., Moon H.I., Lee J.H., et al. Perifollicular fibrosis: pathogenetic role in androgenetic alopecia. Biol Pharm Bull 2006, 29:1246-1250.
44. Randall V.A. Hormonal regulation of hair follicles exhibits a biological paradox. Semin Cell Dev Biol 2007, 18:274-285.
45. Kwack M.H., Sung Y.K., Chung E.J., Im S.U., Ahn J.S., Kim M.K., et al. Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J Invest Dermatol 2008, 128:262-269.
46. Glander H.J., Haidl G., Kohn F.M., Ochsendorf F., Paasch U., Schuppe H.C. Andrology. J Dtsch Dermatol Ges 2007, 5(34):924-933. quiz.
47. Hillmer A.M., Brockschmidt F.F., Hanneken S., Eigelshoven S., Steffens M., Flaquer A., et al. Susceptibility variants for male-pattern baldness on chromosome 20p11. Nat Genet 2008, 40:1279-1281.
48. Richards J.B., Yuan X., Geller F., Waterworth D., Bataille V., Glass D., et al. Male-pattern baldness susceptibility locus at 20p11. Nat Genet 2008, 40:1282-1284.
49. McGaughran J.M., Oates A., Donnai D., Read A.P., Tassabehji M. Mutations in PAX1 may be associated with Klippel-Feil syndrome. Eur J Hum Genet 2003, 11:468-474.