Minoxidil and male-pattern alopecia: a potential role for a local regulator of sebum secretion with vasoconstrictive effects?

Regulation of the hair cycle takes place at the pilo-sebaceous unit with th e sebaceous gland as a sex hormone-dependent part Although minoxidil stimulates proliferation of follicular cells and activat ion of prostaglandin endoperoxide synthase-l, it was suggested that other m echanisms, such as an increase in the local blood flow, might mediate the d rug effect on hair growth. If that is the case, it is possible that minoxid il counteracts some vasoconstrictive mediator of male-pattern alopecia. This hypothetical vasoconstrictive media for X would have to meet some crit eria: (I) vasoconstriction both in the general circulation and in the hair- growing skin; (II) local vasoconstrictive activity in the hair growing skin should be related to the circulating testosterone level; (III) only an inc rease in the local mediator X activity causes male-pattern alopecia, since hypertensive patients are not balder than expected. The sebaceous gland is a possible place of the mediator X secretion since i t is a sex-hormone-dependent part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the media for X, since male hormones raise ET-1 p lasma levels and female hormones lower them. The speculation presented here is that ET-1, beside vasoconstriction in the general circulation, might also regulate the sebum secretion, by triggerin g contractions of the myoepithelial cells. This hypothetical mechanism woul d normally remain confined to the sebaceous gland. During puberty, sex horm ones stimulate growth of sebaceous glands in both sexes. In women hypertrop hied sebaceous glands under estrogen control would not increase its ET-1 co ntent, while in men, testosterone would increase ET-1 secretion that might affect the neighboring arterioles. Induced vasoconstriction might reduce th e hair growth and promote hair loss. If ET-I plays the described role, then an ET-1 antagonist, i.e. bosentane, should also have some hair-growing properties. (C) 1999 Harcourt Publishers Ltd.