Telogen hair follicles are very short in length. They are characterised by a lack of pigment-producing melanocytes and the inner root sheath. Their compact ball-shaped dermal papilla is closely attached to a small cap of secondary hair germ keratinocytes containing hair follicle stem cells. A balance of local growth stimulators and inhibitors in the proximal part of the telogen hair follicle appears to be critical for the initiation of the telogen-anagen transition. In particular, activation of the Shh pathway induces hair follicle transition from telogen to anagen [56]. The high sensitivity of telogen hair follicles to Shh pathways was confirmed by the initiation of anagen by a single topical application of synthetic, non – peptidyl small molecule agonists of the Hh pathway [57]. On the other hand, telogen skin has been suggested to contain inhibitors of hair growth [58]. Bone morphogenetic protein 4 (BMP4) has been identified as one of these inhibitors, as antagonising the BMP4 pathway by its endogenous inhibitor, noggin, induces active hair growth in post-natal telogen skin in vivo [26]. Interestingly, noggin increased Shh mRNA in the hair follicle, while BMP4 downregulated Shh [26].
Cell proliferation in the germinative compartment of the telogen hair follicle can also be activated by applying mechanical or chemical stimuli. For instance, removing the hair shaft from telogen follicles by epilation results in a new hair growth wave [59]. The molecular mechanisms underlying this induction remain largely unknown. However, plucking-induced anagen is widely used as a model for studying the hair cycle in mice to evaluate the expression pattern of genes of interest at distinct hair cycle stages, although there is always the possibility of abnormal effects due to the wounding caused by plucking. In addition, telogen – anagen transformation of mouse hair follicles can also be induced by the administration of immunosuppressants such as cyclosporin A and FK506 [60,61]. Indeed, the stimulation of unwanted hair growth is one of the most common dermatological side effects of immunosuppressive cyclosporine A therapy, seen in transplantation medicine and in the treatment of autoimmune diseases [62].