The Endocrine Control of the Hair Follicle

  • Valerie A. Randall


• Hair follicles can produce different types of hair (length, thickness, colour) at various times in an individual’s life due to the follicle’s capacity to regenerate a new hair during the hair cycle. This allows hairs to change to correlate with alterations in season or sexual development, etc.

• The type of hair produced is under endocrine control with androgens being key regulators of human hair growth; several other hormones are involved, particularly in other mammals, including melatonin, prolactin, melanocyte-stimulating hormone (MSH) and oestrogens.

• Androgens have paradoxically different effects on human hair follicles depending on their body site. This ranges from stimulation, e.g. on the face, axilla, pubis and chest, through no effect on the eyelashes, to inhibition on parts of the scalp, causing balding in genetically susceptible individuals.

• All androgen effects require an intracellular androgen receptor in the hair follicle cells and most, except for pubic and axillary follicles, also require the intracellular enzyme 5α-reductase type 2 to metabolize testosterone to its more potent metabolite 5α- dihydrotestosterone.

• Exactly how androgens regulate hair follicles is not fully established, but most aspects appear to be coordinated via the mesenchyme-derived dermal papilla situated at the base of the follicle. In the current hypothesis androgens from the blood bind to androgen receptors in dermal papilla cells, altering their gene expression, particularly of paracrine signalling molecules, which influence the activity of the other follicular cells. Key signals identified so far include insulin-like growth factor-1 (IGF-1) in growth stimulation and transforming growth factor-β (TGF-β) in inhibition.

• Androgen-dependent hair disorders are not easily controlled. Currently, antiandrogens, such as cyproterone acetate or spironolactone, can be used for hirsutism in women and 5α-reductase type 2 inhibitors, such as finasteride, for androgenetic alopecia. The most common non-endocrine treatment for hair loss is minoxidil, a vasoactive drug. Further understanding of the mechanism of androgen action in hair follicles should lead to the development of better treatments.


Androgen Receptor Hair Follicle Hair Growth Human Hair Scalp Hair 
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  1. 1.
    Ando Y, Yamaguchi Y, Hamada K et al (1999) Expression of mRNA for androgen receptor, 5α-reductase and 17β-hydroxysteroid dehydrogenase in human dermal papilla cells. Br J Dermatol 141:840–845 PubMedCrossRefGoogle Scholar
  2. 2.
    Asada Y, Sonoda T, Ojiro M et al (2001) 5α-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 PubMedCrossRefGoogle Scholar
  3. 3.
    Carey AH, Chan KL, Short F et al (1993) Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol 38:653–658 CrossRefGoogle Scholar
  4. 4.
    Chanda S, Robinette CL, Couse JF et al (2000) 17beta-estradiol and ICI-182780 regulate the hair follicle cycle in mice through an estrogen receptor-alpha pathway. Am J Physiol 278:E202–E210 Google Scholar
  5. 5.
    Chieffi M (1949) Effect of testosterone administration on the beard growth of elderly males. J Gerontol 4:200–204 PubMedGoogle Scholar
  6. 6.
    Conrad F, Ohnemus U, Bodo E et al (2004) Estrogens and human scalp hair growth – still more questions than answers. J Invest Dermatol 122:840–842PubMedCrossRefGoogle Scholar
  7. 7.
    Courtois M, Loussouarn G, Howseau S et al (1996) Periodicity in the growth and shedding of hair. Br J Dermatol 134:47–54 PubMedCrossRefGoogle Scholar
  8. 8.
    Davies GC, Thornton MJ, Jenner TJ et al (2005) Novel and established potassium channel openers stimulate hair growth in vitro: implications for their modes of action in hair follicles. J Invest Dermatol 125:686–694 CrossRefGoogle Scholar
  9. 9.
    Ebling FG, Hale PA, Randall VA (1991) Hormones and hair growth. In: Goldsmith LA (ed) Biochemistry and physiology of the skin, 2nd edn. Clarendon, Oxford, pp 660–690Google Scholar
  10. 10.
    Eckert J, Church RE, Ebling FJ et al (1967) Hair loss in women. Br J Dermatol 79:543–548 PubMedCrossRefGoogle Scholar
  11. 11.
    Elliot K, Stephenson TJ, Messenger AG (1999) Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses. J Invest Dermatol 113:873–877CrossRefGoogle Scholar
  12. 12.
    Ellis JA, Stebbing M, Harrap SB (2000) Polymorphism of androgen receptor gene is associated with male pattern baldness. J Invest Dermatol 116:452–455.CrossRefGoogle Scholar
  13. 13.
    Fiotzik K, Krause K, Conrad F et al (2006) Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Am J Pathol 168:748–756 CrossRefGoogle Scholar
  14. 14.
    Girman CJ, Rhodes T, Lilly FRW et al (1998) Effects of self-perceived hair loss in a community sample of men. Dermatology 197:223–229 PubMedCrossRefGoogle Scholar
  15. 15.
    Hamada K, Randall VA (2006) Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness Br J Dermatol 154:609–618PubMedCrossRefGoogle Scholar
  16. 16.
    Hamilton JB (1951) Patterned loss of hair in man; types and incidence. Ann NY Acad Sci 53:708–728 PubMedCrossRefGoogle Scholar
  17. 17.
    Hamilton JB (1958) Age, sex and genetic factors in the regulation of hair growth in man: a comparison of Caucasian and Japanese populations. In: Montagna W, Ellis RA (eds) The biology of hair growth. Academic Press, New York, pp 399–433 Google Scholar
  18. 18.
    Hamilton JB (1960) Effect of castration in adolescent and young adult males upon further changes in the proportions of bare and hairy scalp. J Clin Endocrinol Metabol 20:1309–1318 CrossRefGoogle Scholar
  19. 19.
    Handelsman D J (2005) Androgen action and pharmacologic uses. In: DeGroot LJ, Jameson J L (eds) Endocrinology, 5th edn. WB Saunders, Philadelphia, pp 3121–3138 Google Scholar
  20. 20.
    Hibberts NA, Howell AE, Randall VA (1998) Dermal papilla cells from human balding scalp hair follicles contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol 156:59–65 PubMedCrossRefGoogle Scholar
  21. 21.
    Hibberts NA, Messenger AG, Randall VA (1996) Dermal papilla cells derived from beard hair follicles secrete more stem cell factor (SCF) in culture than scalp cells or dermal fibroblasts. Biochem Biophys Res Commun 222:401–405PubMedCrossRefGoogle Scholar
  22. 22.
    Hibino T, Nishiyama T (2004) Role of TGF-β2 in the human hair cycle. J Dermatol Sci 35:9–18 PubMedCrossRefGoogle Scholar
  23. 23.
    Ibanez L, Ong KK, Mongan N et al (2003) Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism. J Clin Endocrinol Metab 88:3333–3338 PubMedCrossRefGoogle Scholar
  24. 24.
    Inui S, Fukuzato Y, Nakajima F et al (2002) Androgen-inducible TGFbeta1 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 PubMedGoogle Scholar
  25. 25.
    Itami S, Kurata S, Sonada T et al (1995) Interactions between dermal papilla cells and follicular epithelial cells in vitro: effect of androgen. Br J Dermatol 132:527–532 PubMedGoogle Scholar
  26. 26.
    Jahoda CA, Oliver RF, Reynolds AJ et al (2001) Trans-species hair growth induction by human hair follicle dermal papillae. Exp Dermatol 10:229–237 PubMedCrossRefGoogle Scholar
  27. 27.
    Jave-Suarez L F, Langbein L, Winter H et al (2004) Androgen regulation of the human hair follicle: the type 1 hair keratin hHa7 is a direct target gene in trichocytes. J Invest Dermatol 122:555–564 PubMedCrossRefGoogle Scholar
  28. 28.
    Kaufman KD, Olsen EA, Whiting D et al (1988) Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol 39:578–589 CrossRefGoogle Scholar
  29. 29.
    Kligman AG (1959) The human hair cycle. J Invest Dermatol 33:307–316 PubMedGoogle Scholar
  30. 30.
    Kim CD, Choe Y, Shim C et al (2002) Interferon-β secreted from human hair dermal papilla cells inhibits the growth of outer root sheath cells cultured in vitro. Biochem Biophys Res Commun 290:1133–1138 PubMedCrossRefGoogle Scholar
  31. 31.
    Lincoln GA, Richardson M (1998) Photo-neuroendocrine control of seasonal cycles in body weight, pelage growth and reproduction: lessons from the HPD sheep model. Comp Biochem Physiol Part C 119:283–294 CrossRefGoogle Scholar
  32. 32.
    Liu JP, Baker J, Perkins AS et al (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor 1 (IGF-1) and type 1 IGF receptor (IGF 1r). Cell 75:59–72 PubMedGoogle Scholar
  33. 33.
    Ludwig E (1977) Classification of the types of androgenic alopecia (common baldness) arising in the female sex. Br J Dermatol 97:249–256 CrossRefGoogle Scholar
  34. 34.
    Lynfield YL (1960) Effect of pregnancy on the human hair cycle. J Invest Dermatol 35:323–327 PubMedGoogle Scholar
  35. 35.
    Marshall WA, Tanner JM (1969) Variations in pattern of pubertal change in girls. Arch Dis Child 44:291–303PubMedGoogle Scholar
  36. 36.
    Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23PubMedGoogle Scholar
  37. 37.
    Matias JR, Malloy V, Orentreich N (1989) Animal models of androgen-dependent disorders of the pilosebaceous apparatus. Arch Dermatol Res 281:247–253 PubMedCrossRefGoogle Scholar
  38. 38.
    McPhaul MJ (2005) Mutations that alter androgen function; androgen insensitivity and related disorders. In: Degroot LJ, Jameson JL (eds) Endocrinology, 5th ed., Section XIV. In: Burger HG (ed) Male reproduction. WB Saunders, Philadelphia, pp 3139–3157 Google Scholar
  39. 39.
    Midorikawa T, Chikazawa T, Yoshino T et al (2004) Different gene expression profile observed in dermal papilla cells related to androgenic alopecia by DNA macroarray analysis. J Dermatol Sci 36:25–32 PubMedCrossRefGoogle Scholar
  40. 40.
    Mou C, Jackson B, Schneider P et al (2006) Generation of the primary hair follicle pattern. Proc Natl Acad Sci USA 103:9075–9080 PubMedCrossRefGoogle Scholar
  41. 41.
    Oh H-S, Smart RC (1996) An estrogen receptor pathway regulates the telogen-anagen hair follicle transition and influences epidermal cell proliferation. Proc Natl Acad Sci USA 93:12525–12530PubMedCrossRefGoogle Scholar
  42. 42.
    Orentreich N (1969) Scalp hair replacement in men. In: Montagna W, Dobson RL (eds) Advances in biology of skin, vol 9. Hair growth. Pergamon, Oxford, pp 99–108 Google Scholar
  43. 43.
    Orentreich N, Durr NP (1982) Biology of scalp hair growth. Clin Plast Surg 9:197–205 PubMedGoogle Scholar
  44. 44.
    Philpott M (2000) The roles of growth factors in hair follicles: investigations using cultured hair follicles. In: Camacho FM, Randall VA, Price VH (eds) Hair and its disorders: biology, pathology and management. Martin Dunitz, London, pp 103–113 Google Scholar
  45. 45.
    Philpott MP, Sanders DA, Kealey T (1994) Effects of insulin and insulin-like growth factors on cultured human hair follicles; IGF-1 at physiologic concentrations is an important regulator of hair follicle growth in vitro. J Invest Dermatol 102:857–861PubMedCrossRefGoogle Scholar
  46. 46.
    Randall VA (1994) Androgens and human hair growth. Clin Endocrinol 40:439–457CrossRefGoogle Scholar
  47. 47.
    Randall VA (1994) The role of 5α-reductase in health and disease. In: Sheppard M, Stewart P (eds) Hormones, enzymes and receptors. Baillières Clin Endocrinol Metabol 8:405–431 Google Scholar
  48. 48.
    Randall VA (2000) Androgens: the main regulator of human hair growth. In: Camacho FM, Randall VA, Price VH (eds) Hair and its disorders: biology, pathology and management. Martin Dunitz, London, pp 69–82 Google Scholar
  49. 49.
    Randall VA (2001) Is alopecia areata an autoimmune disease? Lancet 358:1922–1924 PubMedCrossRefGoogle Scholar
  50. 50.
    Randall VA (2004) Androgens and hair: a biological paradox. In: Nieschlag E, Behre HM, (eds) Testosterone: action, deficiency, substitution, 3rd edn Cambridge University Press, Cambridge, pp 207–231Google Scholar
  51. 51.
    Randall VA (2005) Physiology and pathophysiology of androgenetic alopecia. In: Degroot LJ, Jameson JL (eds) Endocrinology, 5th edn., Section XIV. In: Burger HG (ed) Male reproduction. WB Saunders, Philadelphia, pp 3295–3309 Google Scholar
  52. 52.
    Randall VA (2007) Hormonal regulation of hair follicles exhibits a biological paradox. Semin Cell Dev Biol 18(2):274–285 PubMedCrossRefGoogle Scholar
  53. 53.
    Randall VA, Ebling EJG (1991) Seasonal changes in human hair growth. Br J Dermatol 124:146–151 PubMedCrossRefGoogle Scholar
  54. 54.
    Randall VA, Hibberts NA, Hamada K (1996) A comparison of the culture and growth of dermal papilla cells derived from normal and balding (androgenetic alopecia) scalp. Br J Dermatol 134:437–444 PubMedCrossRefGoogle Scholar
  55. 55.
    Randall VA, Sundberg JP, Philpott MP (2003) Animal and in vitro models for the study of hair follicles. J Investig Dermatol Symp Proc 8:39–45 PubMedCrossRefGoogle Scholar
  56. 56.
    Randall VA, Thornton MJ, Hamada K et al (1991) Androgens and the hair follicle: cultured human dermal papilla cells as a model system. Ann NY Acad Sci 642:355–375 PubMedCrossRefGoogle Scholar
  57. 57.
    Randall VA, Thornton MJ, Messenger AG (1992) 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 3:141–147 Google Scholar
  58. 58.
    Reinberg A, Smolensky MH, Hallek M et al (1988) Annual variation in semen characteristics and plasma hormone levels in men undergoing vasectomy. Fertil Steril 49:309–315 PubMedGoogle Scholar
  59. 59.
    Rendl M, Lewis L, Fuchs E (2005) Molecular dissection of mesenchymal–epithelial interactions in the hair follicle. PloS Biol 3(11):e331 PubMedCrossRefGoogle Scholar
  60. 60.
    Reynolds AJ, Jahoda CAB (2004) Cultured human and rat tooth papilla cells induce hair follicle regeneration and fibre growth. Differentiation 72:566–575PubMedCrossRefGoogle Scholar
  61. 61.
    Reynolds AJ, Lawrence C, Cserhalmi-Friedman PB et al (1999) Trans-gender induction of hair follicles. Nature 402:33–34 PubMedCrossRefGoogle Scholar
  62. 62.
    Rutberg SE, Kolpak ML, Gourley JA et al (2006) Differences in expression of specific biomarkers distinguish human beard from scalp dermal papilla cells. J Invest Dermatol 126(12):2583–2595PubMedCrossRefGoogle Scholar
  63. 63.
    Saitoh M, Sakamoto M (1970) Human hair cycle. J Invest Dermatol 54:65–81 PubMedCrossRefGoogle Scholar
  64. 64.
    Sawers RA, Randall VA, Iqbal MJ (1982) Studies on the clinical and endocrine aspects of antiandrogens. In: Jeffcoate JL (ed) Androgens and antiandrogen therapy. Curr Top Endocrinol 1: 145–168 Google Scholar
  65. 65.
    Sonada T, Asada Y, Kurata S et al (1999) The mRNA for protease nexin-1 is expressed in human dermal papilla cells and its level is affected by androgen. J Invest Dermatol 113:308–313 CrossRefGoogle Scholar
  66. 66.
    Tang L, Bernardo O, Bolduc C et al (2003) The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia. J Am Acad Dermatol 49:229–233PubMedCrossRefGoogle Scholar
  67. 67.
    Thornton MJ, Hibberts NA, Street T et al (2001) Androgen receptors are only present in mesenchyme-derived dermal papilla cells of red deer (Cervus elaphus) neck follicles when raised androgens induce a mane in the breeding season. J Endocrinol 168:401–408 PubMedCrossRefGoogle Scholar
  68. 68.
    Thornton MJ, Nelson LD, Taylor AH et al (2006) The modulation of aromatase and estrogen receptor alpha in cultured human dermal papilla cells by dexamethasone: a novel mechanism for selective action of estrogen via estrogen receptor beta? J Invest Dermatol 126:2010–2018PubMedCrossRefGoogle Scholar
  69. 69.
    Thornton MJ, Taylor AH, Mulligan K et al (2003) The distribution of estrogen receptor beta is distinct to that of estrogen receptor alpha and the androgen receptor in human skin and the pilosebaceous unit. J Investig Dermatol Symp Proc 8:100–103PubMedCrossRefGoogle Scholar
  70. 70.
    Uno H, Imamura K, Pan H (2000) Androgenetic alopecia in the stump-tailed macaque. An important model for investigating the pathology and antiandrogenetic therapy of male pattern baldness. In: Camacho F, Randall VA, Price V (eds) Hair and its disorders: biology, pathology and management. Martin Dunitz, London, pp 137–151Google Scholar
  71. 71.
    Van Neste D, de Brouwer B (2000) Human hair follicle grafts in nude mice. An important in vivo model for investigating the control of hair growth. In: Camacho F, Randall VA, Price V (eds) Hair and its disorders: biology, pathology and management. Martin Dunitz, London, pp 115–119Google Scholar
  72. 72.
    Van Scott EJ, Ekel TM (1958) Geometric relationships between the matrix of the hair bulb and its dermal papilla in normal and alopecic scalp. J Invest Dermatol 31:281–287 Google Scholar
  73. 73.
    Wehr TA, Giesen HA, Moul DE et al (1995) Suppression of men’s responses to seasonal changes in day length by modern artificial lighting. Am J Physiol 269:R173–R178PubMedGoogle Scholar
  74. 74.
    Wilson JD, Griffin JE, Russell DW (1993) Steroid 5α-reductase 2 deficiency. Endocr Rev 14:577–593 PubMedCrossRefGoogle Scholar
  75. 75.
    Wu-Kuo T, Chuong C-M (2000) Developmental biology of hair follicles and other skin appendages. In: Camacho FM, Randall VA, Price VH (eds) Hair and its disorders: biology, pathology and management. Martin Dunitz, London, pp 17–37Google Scholar

Copyright information

© Springer London 2008

Authors and Affiliations

  • Valerie A. Randall
    • 1
  1. 1.Division of Biomedical SciencesUniversity of BradfordWest YorkshireUK

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