Hair follicle pigmentation

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.

Figure 1. Melanocyte distribution in the human anagen scalp hair follicle.

Melanocytes in frozen scalp sections were detected using the antibody against gp100. Epi-MC, epidermal melanocytes; IFD-Mc, infundibular melanocytes; SG-Mc, sebaceous gland melanocytes; ORS-Mc, outer root sheath melanocytes; Mel-BMc, melanogenic bulbar melanocytes; Amel-BMc, amelanotic bulbar melanocytes; DP, dermal papilla.

Figure 2 (Fig S2). Biophysical characteristics of rodent hairs.

Electron paramagnetic resonance spectrometry signals show eumelanin character (A) and pheomelanin (B) contribution of the hair shaft pigments. Bars on the right above each spectrum show relative free-radical (melanin) concentration per 20 mg of dry fur. Pheomelanin contribution is further quantified by the a/b ratio (see hyperfine splitting of the EPR signal in B). Position of the free-radical standard 1,1-diphenyl-2-picrylhydrazyl (DPPH; g = 2.0037) is indicated by the arrow. All the spectra were registered at room temperature at X-band (9.2 GHz), 1 mW microwave power, 2 Gs modulation amplitude, and variable gain (dopa melanin, C57BL/6J a/a—12,500; cysteinyldopa melanin 62,000; agouti hamster—320,000; brown DBA/2, and C57BL/6J A^y/a – 400,000; other samples—800,000); for bar plots (means of n = 5 ± SEM) modulation amplitude was 5 Gs, and all the integral amplitudes were recalculated for the constant gain 12,500.