Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles

Abstract

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocytelineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.

Potential Involvement of the Stem Cell Factor Receptor c-kit in Alopecia Areata and Androgenetic Alopecia: Histopathological, Immunohistochemical, and Semiquantitative Investigations

“…The binding of SCF to c-kit transactivates the receptor tyrosine kinase to activate stem cells, and the SCF/c-kit signaling induces cell survival, differentiation, and proliferation; the latter is evidenced by the cell proliferation marker Ki-67 [8, 18, 30]. In the hair follicle, the cells of the keratinocytic and melanocytic lineage are responsible for hair growth and color, respectively, and express c-kit [4, 25, 26, 29], while stromal cells in the dermis produce SCF [4, 28]. Thus, it is conjectured that the SCF/c-kit signaling is involved in the pathological processes of AAR and AGA.…”

Androgens and ageing of the skin

“…During ageing, androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle. The stem cell factor (SCF)/c-Kit signalling pathway, which is important in embryonic melanocyte migration and maintaining adult rodent pigmentation has been suggested to be involved in this process [48 ]. In addition, it has been demonstrated that androgens lead to changes in transcription of genes in the DPC, which regulate hair growth and the hair growth cycle [49,50].…”

Comparative study of efficacy of epidermal melanocyte transfer versus hair follicular melanocyte transfer in stable vitiligo

“…They are localized in the outer layer of the outer root sheath of the infundibulum and midfollicle and the matrix of the hair bulb. [7] Comparison of epidermal and follicular melanin units[8] reveals that there are certain important differences between both of them. The ratio between keratinocytes and melanocytes is 1:6 in hair follicle whereas it is 1:36 in epidermis.…”