Minoxidil: Mechanisms of Action on Hair Growth

A.G. Messenger; J. Rundegren

Disclosures

The British Journal of Dermatology. 2004;150(2) 

In This Article

Conclusions

The emergence of topical minoxidil for the treatment of androgenetic alopecia in the early 1980s led to the realization that hair loss is potentially treatable and ushered in a new era in hair research. The series of experiments by Buhl and others on cultured vibrissae follicles and on the stumptail macaque support the view that the hair follicle response to minoxidil is mediated by its sulphated metabolite acting as a potassium channel opener. Nevertheless there are inconsistencies in the results that have yet to be resolved and this idea must be viewed as unproven. A variety of responses to minoxidil have been described in cultured cells. Some have potential relevance to hair growth, such as the effects on cell growth and senescence and the stimulation of VEGF and prostaglandin synthesis. Others, such as the effects on collagen synthesis, are more difficult to explain. Viewed in isolation, the results of cell culture studies must be interpreted with care. First, the relationship between the complexities of hair growth and the behaviour of a single cell type cultured in a Petri dish is uncertain. Second, the concentrations of minoxidil used have often exceeded those to which the hair follicle is likely to be exposed in vivo. Blood levels in subjects taking minoxidil orally are in the upper nanomolar/low micromolar range (20-2000 ng mL-1) and are lower still in those using minoxidil topically (~ 2 ng mL-1). Third, the minoxidil target cell population in the hair follicle is unknown. Nevertheless, the stimulation of VEGF and prostaglandin synthesis by minoxidil in dermal papilla cells provides an attractive and logical starting point for future studies and is backed up by evidence from other sources. We need to know more about the signalling mechanisms responsible for these effects -- do they involve conventional potassium channel physiology or a novel mechanism as suggested by Li et al.?[41] Are KATP channels operating in the regulation of normal hair growth or the development of androgenetic alopecia and, if so, what is their subtype composition and cellular and subcellular distribution?

Why is minoxidil important? Although the benefits in androgenetic alopecia have been demonstrated in clinical trials, there is perhaps a tendency to dismiss the significance of minoxidil. Yet, it remains the only medical treatment of proven efficacy when used topically and is the only treatment approved for hair loss in women. Minoxidil affects hair cycling, causing premature termination of telogen and probably prolonging anagen. Understanding how minoxidil exerts these effects may lead not only to better treatments for hair loss but also will increase our understanding of the mechanisms responsible for controlling the hair cycle.


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