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Inhibition of human hair follicle growth by endo- and exocannabinoids

Andrea Telek^*,,1, Tamás Bíró^*,,1,2, Enik Bodó, Balázs I. Tóth^*,2, István Borbíró^*, George Kunos and Ralf Paus

^* Department of Physiology and

Cell Physiology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary;

Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, Lübeck, Germany; and

National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA

²Correspondence: Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO Box 22, 4032 Debrecen, Hungary. E-mail: biro{at}phys.dote.hu

Recent studies strongly suggest that the cannabinoid system is a key player in cell growth control. Since the organ-culture of human hair follicles (HF) offers an excellent, clinically relevant model for complex tissue interaction systems, we have asked whether the cannabinoid system plays a role in hair growth control. Here, we show that human scalp HF, intriguingly, are both targets and sources of endocannabinoids. Namely, the endocannabinoid N-arachidonoylethanolamide (anandamide, AEA) as well as the exocannabinnoid (9) -tetrahydrocannabinol dose-dependently inhibited hair shaft elongation and the proliferation of hair matrix keratinocytes, and induced intraepithelial apoptosis and premature HF regression (catagen). These effects were inhibited by a selective antagonist of cannabinoid receptor-1 (CB1). In contrast to CB2, CB1 was expressed in a hair cycle-dependent manner in the human HF epithelium. Since we successfully identified the presence of endocannabinoids in human HF, our data strongly suggest that human HF exploit a CB1-mediated endocannabinoid signaling system for negatively regulating their own growth. Clinically, CB1 agonists may therefore help to manage unwanted hair growth, while CB1 antagonists might counteract hair loss. Finally, human HF organ culture offers an instructive, physiologically relevant new research tool for dissecting "nonclassical" effects of endocannabinoids and their receptor-mediated signaling in general.—Telek, A., Bíró, T., Bodó, E., Tóth, B. I., Borbíró, I., Kunos, G., Paus, R. Inhibition of human hair follicle growth by endo- and exocannabinoids.

Key Words: cannabinoid receptor • proliferation • apoptosis • hair cycle

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