F1  MECHANISMS OF ACTION OF MINOXIDIL AS A HAIR GROWTH STIMULATOR: OPEN QUESTIONS, HYPOTHETICAL CONCEPTS

Paus R., Dept. of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany.

Minoxidil (M), a potassium channel opener, can stimulate hair re-growth in men and women with androgenetic alopecia by inducing and/or prolonging anagen as well as by stimulating a vellus-to-terminal hair conversion. M sulfate is the active metabolite, and a major M effect on androgen metabolism is unlikely. Yet, besides the elusive underlying mechanisms of action (e.g., are the potassium channel effects of M are related to its hair growth effects?), the key target cell population for M activity remains unclear. Given that M increases capillary fenestration in the follicular vasculature and up-regulates the expression of angiogenic factors such as VEGF and HGF it deserves careful re-consideration whether the hair growth-stimulatory effects of M - in appropriately susceptible individuals -are mainly endothelial cell-and/or perfusion-mediated. Also, direct effects on hair follicle keratinocyte mitosis and proliferative potential as well as on morphogen secretion by DP fibroblasts (e.g. HGF, IGF-1, KGF?) must be taken into account. It remains to be dissected whether M down-modulates endogenous key inhibitors of hair growth (e.g. BMPs, TGFß, neurotrophins?), and what distinguishes M responders from non-responders (M sulfotransferase activity?). Whether the reported DP fibroblast-cytoprotective effects of  M are clinically important at all remains to be shown. The same is true for the reported inhibitory effect of M on collagen synthesis and lysyl hydroxylase activity as well as the stimulation of metalloproteinase-2 expression by M,  which have been speculated to counter-act perifollicular fibrosis in androgenetic alopecia. However, these recently surfaced M targets promise that answers to the open questions listed above are within our reach.