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

• Published in: Medical hypotheses Vol. 53; no. 5; pp. 402 - 406
• Main Authors: Kurbel, S., Kurbel, B., Žanić-Matanić, D.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-11-1999; Elsevier
• Subjects: Alopecia - blood; Alopecia - drug therapy; Biological and medical sciences; Endothelin-1 - pharmacology; Estrogens - blood; Humans; Male; Medical sciences; Minoxidil - pharmacology; Minoxidil - therapeutic use; Models, Theoretical; Pharmacology. Drug treatments; Sebum - secretion; Skin, nail, hair, dermoskeleton; Testosterone - blood; Vasoconstriction - drug effects; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use; Human; Skin disease; Endothelin; Secretion; Peptide hormone; Vasoconstriction; Male; Sebum; Minoxidil; Hair (head); Regulation(control); Treatment; Piperidine derivatives; Vasoconstrictor agent; Mechanism of action; Androgenetic alopecia
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1054/mehy.1998.0793

Regulation of the hair cycle takes place at the pilo-sebaceous unit with the sebaceous gland as a sex hormone-dependent part.
Although minoxidil stimulates proliferation of follicular cells and activation of prostaglandin endoperoxide synthase-1, it was suggested that other mechanisms, such as an increase in the local blood flow, might mediate the drug effect on hair growth. If that is the case, it is possible that minoxidil counteracts some vasoconstrictive mediator of male-pattern alopecia.
This hypothetical vasoconstrictive mediator X would have to meet some criteria: (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 increase 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 it is a sex-hormone-dependent part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the mediator X, since male hormones raise ET-1 plasma 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 triggering contractions of the myoepithelial cells. This hypothetical mechanism would normally remain confined to the sebaceous gland. During puberty, sex hormones stimulate growth of sebaceous glands in both sexes. In women hypertrophied sebaceous glands under estrogen control would not increase its ET-1 content, while in men, testosterone would increase ET-1 secretion that might affect the neighboring arterioles. Induced vasoconstriction might reduce the hair growth and promote hair loss.
If ET-1 plays the described role, then an ET-1 antagonist, i.e. bosentane, should also have some hair-growing properties.