Oligonucleotide treatment increases eumelanogenesis, hair pigmentation and melanocortin‐1 receptor expression in the hair follicle

Abstract
Abstract:  It was previously reported that telomere homologue oligonucleotides (T‐oligos) can induce a variety of cellular responses in skin including increased melanogenesis. To assess the effects of T‐oligos on hair pigmentation, we administered thymidine dinucleotide (pTT), one‐third of the TTAGGG telomere repeat sequence, intradermally at distinct time points of the depilation‐induced hair cycle in C3H/HeJ mice. Penetration of T‐oligos into the hair follicle (HF) was monitored by using FITC‐labelled pTT and confocal microscopy. pTT treatment on days 1–5 after depilation, during early anagen, did not significantly alter the number and proliferation of melanocytes (Trp‐2‐positive cells), compared with vehicle‐treated controls. However, pTT treatment on days 5–12 after depilation, during mid‐ to late anagen, resulted in the formation of darker hairs, that showed a significantly increased eumelanin/total melanin ratio in their sub‐apical agouti band region, compared with vehicle‐treated controls (P < 0.05). By RT‐PCR and western blot, full thickness skin of pTT‐treated mice showed increases in Trp‐1, Trp‐2 and tyrosinase mRNA and protein levels, compared with control mice. Western blot analyses of two receptors that positively regulate eumelanogenesis, melanocortin type 1 receptor (MC‐1R) and kit, showed increased expression of MC‐1R protein in pTT‐treated versus control skin, while the levels of c‐kit receptor remained unchanged. These data demonstrate that pTT treatment increases eumelanogenesis in HFs, associated with increased tyrosinase, TRP‐1 and MC‐1R expression. These data also raise the possibility of using T‐oligos to modulate hair pigmentation.