Hair growth-modulation by adrenergic drugs

Since we have recently shown that the beta 2-adrenoreceptor (beta 2-AR) expression of selected regions of the hair follicle (HF) epithelium as well as the number of adrenergic nerve fibers in murine skin change in a hair cycle-dependent manner, this has raised the possibility that adrenergic nerves may exert "trophic" functions during HF cycling. To further explore this concept, we have investigated the effect of neuro-pharmacological manipulations on hair growth (anagen) induction in quiescent telogen mouse skin in vivo. Here, we demonstrate that subcutaneous injections of the noradrenaline (NA)-depleting agent guanethidine, or of the neurotoxin 6-hydroxydopamine, but not of the beta 2-AR agonist isoproterenol induce a premature onset of anagen in the lower back skin of C57BL/6 mice. On day 20 after the start of treatment, more than 80% of the guanethidine-treated mice and ca. 65% of the 6-hydroxydopamine-treated (6-OHDA) mice exhibited premature skin darkening and hair growth at the site of drug application, whereas less than one-third of all control animals showed macroscopic signs of anagen development. This was confirmed by histology, demonstrating mature anagen VI HFs only at the immediate site of treatment with guanethidine or 6-OHDA as opposed to resting telogen HFs in the neighboring untreated skin area. This observation further supports the concept that sympathetic nerves are intimately involved in hair growth control and invites one to explore the neuro-pharmacological manipulation of piloneural interactions as a novel therapeutic strategy for the management of hair growth disorders.