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O#15 Minoxidil
- how does it work?
Andrew Messenger. Dept of Dermatology, Royal
Hallamshire Hospital, Sheffield S10 2JF, UK
The hypertrichotic effect of minoxidil was recognised soon
after it became available for treating hypertension in the
early 1970s. However, despite the passage of 30 years and
major advances in hair biology we still have little understanding
of its mode of action on hair growth.
Initial suggestions that minoxidil stimulates hair growth
by increasing scalp blood flow have not been substantiated
although this remains a possibility. The relaxant property
of minoxidil on vascular smooth muscle is due to the action
of its metabolite, minoxidil sulphate, as a cell surface potassium
channel opener (PCO). Some other PCOs stimulate hair growth
in animal studies and the sulfotransferase enzymes responsible
for minoxidil sulphation are expressed in the hair follicle.
However, attempts to prove that minoxidil stimulates hair
growth by opening potassium channels have met with little
success. In cultured cells of skin or hair follicle origin
minoxidil has been reported to have a variety of other effects.
These include increased cell proliferation or delayed senescence,
stimulation of prostaglandin synthesis, stimulation of VEGF
and inhibition of lysyl hydroxylase. Some of these studies
used concentrations of minoxidil unlikely to be achieved in
vivo and their relevance to hair growth is uncertain. Organ
culture studies have been disappointing. Some studies have
reported the minoxidil increases DNA synthesis in vibrissae
follicle cultures but no clear effect has been observed in
human follicles. The response of human hair growth to topical
minoxidil is very rapid - an increase in hair follicle numbers
occurs within a few weeks - suggesting that minoxidil acts
on the hair cycle to initiate anagen in latent follicles.
This phase of the hair cycle has not been modelled in vitro,
perhaps explaining the lack of response in organ culture experiments.
The pharmacology of minoxidil action on hair growth has not
attracted the attention it deserves. A better understanding
may help to explain aspects of normal hair biology as well
as leading to more effective treatments for hair loss
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