Hair follicle pigmentation.
Journal: 2005/March - Journal of Investigative Dermatology
ISSN: 0022-202X
Abstract:
Hair shaft melanin components (eu- or/and pheomelanin) are a long-lived record of precise interactions in the hair follicle pigmentary unit, e.g., between follicular melanocytes, keratinocytes, and dermal papilla fibroblasts. Follicular melanogenesis (FM) involves sequentially the melanogenic activity of follicular melanocytes, the transfer of melanin granules into cortical and medulla keratinocytes, and the formation of pigmented hair shafts. This activity is in turn regulated by an array of enzymes, structural and regulatory proteins, transporters, and receptors and their ligands, acting on the developmental stages, cellular, and hair follicle levels. FM is stringently coupled to the anagen stage of the hair cycle, being switched-off in catagen to remain absent through telogen. At the organ level FM is precisely coupled to the life cycle of melanocytes with changes in their compartmental distribution and accelerated melanoblast/melanocyte differentiation with enhanced secretory activity. The melanocyte compartments in the upper hair follicle also provides a reservoir for the repigmentation of epidermis and, for the cyclic formation of new anagen hair bulbs. Melanin synthesis and pigment transfer to bulb keratinocytes are dependent on the availability of melanin precursors, and regulation by signal transduction pathways intrinsic to skin and hair follicle, which are both receptor dependent and independent, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. The important regulators are MC1 receptor its and adrenocorticotropic hormone, melanocyte stimulating hormone, agouti protein ligands (in rodents), c-Kit, and the endothelin receptors with their ligands. Melanin itself has a wide range of bioactivities that extend far beyond its determination of hair color.
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J Invest Dermatol 124(1): 13-21

Hair Follicle Pigmentation

Department of Pathology, University of Tennessee, Memphis, Tennessee, USA;
Department of Medicine, Southern Illinois University, Springfield, Illinois, USA;
Department of Biophysics, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland;
Department of Biomedical Sciences, University of Bradford, Bradford, UK;
Institute for Pigmentary Disorders in Association with the Ernst Moritz Arndt University of Greifswald, Greifswald, Germany;
Department of Dermatology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Address correspondence to: Andrzej Slominski, MD, PhD, Department of Pathology and Laboratory, University of Tennessee Health Science Center, 930 Madison Ave, Room 519, Memphis, TN 38163, USA. Email: ude.memtu@iksnimolsa

Abstract

Hair shaft melanin components (eu- or/and pheomelanin) are a long-lived record of precise interactions in the hair follicle pigmentary unit, e.g., between follicular melanocytes, keratinocytes, and dermal papilla fibroblasts. Follicular melanogenesis (FM) involves sequentially the melanogenic activity of follicular melanocytes, the transfer of melanin granules into cortical and medulla keratinocytes, and the formation of pigmented hair shafts. This activity is in turn regulated by an array of enzymes, structural and regulatory proteins, transporters, and receptors and their ligands, acting on the developmental stages, cellular, and hair follicle levels. FM is stringently coupled to the anagen stage of the hair cycle, being switched-off in catagen to remain absent through telogen. At the organ level FM is precisely coupled to the life cycle of melanocytes with changes in their compartmental distribution and accelerated melanoblast/melanocyte differentiation with enhanced secretory activity. The melanocyte compartments in the upper hair follicle also provides a reservoir for the repigmentation of epidermis and, for the cyclic formation of new anagen hair bulbs. Melanin synthesis and pigment transfer to bulb keratinocytes are dependent on the availability of melanin precursors, and regulation by signal transduction pathways intrinsic to skin and hair follicle, which are both receptor dependent and independent, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. The important regulators are MC1 receptor its and adrenocorticotropic hormone, melanocyte stimulating hormone, agouti protein ligands (in rodents), c-Kit, and the endothelin receptors with their ligands. Melanin itself has a wide range of bioactivities that extend far beyond its determination of hair color.

Keywords: follicular melanocytes, hair pigmentation, melanin, melanogenesis
Abbreviations: ASP, agouti protein; BMP, bone morphogenic proteins; COMT, catechol-O-methyltransferase; CRH, corticotropin releasing hormone; CTSL, cysteine protease cathepsin L; DCT, dopa-chrome tautomerase; DHI, dihydroxyindole; DHICA, dihydroxy-indole carboxylic acid; DHICA-CF, DHICA conversion factor; DP, dermal papilla; EPR, electron paramagnetic resonance; ER, endoplasmic reticulum; ET, endothelin; FM, follicular melanogenesis; l-dopa; l-3,4-dihydroxyphenylalanine; MC1, melanocortin receptor 1; MIF, macrophage migration inhibitory factor; MITF, microphtalmia-associated transcription factor; MRP, melanogenesis-related proteins; MSH, melanocyte stimulating hormone; OCA, oculocutaneous albinism; PAH, phenylalanine hydroxylase; PAR2, protease-activated receptor 2; ROS, reactive oxygen species; SCF, stem cell factor; TGN, trans-Golgi network; TRP, tyrosinase-related protein
Abstract

Footnotes

Supplementary Material

The following material is available from http://www.blackwellpublishing.com/products/journals/suppmat/JID/JID23528/JID23528sm.htm

Figure S1 Scheme illustrating common pathway for follicular and epidermal melanogenesis. GSH, glutathione; Cys, cysteine; 1, phenylalanine hydroxylation; 2, tyrosine hydroxylation; 3, dopa oxidation; 4, dopa-chrome tautomerization; 5a, dihydroxyindole carboxylic acid (DHICA) oxidation; 5b, dihydroxyindole (DHI) oxidation; A, hydrolysis of glutathionyldopa; B, oxidation of cysteinyldopa; C, intramolecular cyclization of cysteinyldopaquinone.

Figure S2 Biophysical characteristics of rodent hairs (color version). For explanation, see Fig 2 legend in the text.

Table S1. Characteristics of melanocytes in human and murine anagen hair follicles. Recently low expression of tyrosine hydroxylase mRNA or its absence was reported in one study that used RT-PCR methodology (S23). However, these authors did not measure the actual enzyme activity and they cannot entirely exclude alternative splicing mechanism as the reason for the negative results. Thus, further experimentation is necessary to reconcile these differences.

References S1–S23

Slominski A, Plonka PM, Pisarchik A, Smart JL, Tolle V, Wortsman J, Low MJ: Preservation of eumelanin hair pigmentation in POMC-gene knockout mice on a non-agouti (a/a) genetic background. Submitted for publication, 2004.

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