Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and TGF-beta2-/IGF-1-mediated regulation of hair cycle in male and female human hair follicles in vitro.

Abstract

BACKGROUND: Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). OBJECTIVES: We aimed at investigating the impact of caffeine a) on additional key hair growth parameters, b) on major hair growth-regulatory growth factors and c) on male versus female HFs in the presence of testosterone. METHODS: Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0,5 mug/ml) or in combination with caffeine (0.005-0.0005%), and effects on hair shaft elongation, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and expression of a key catagen inducer, transforming growth factor beta2 (TGF-beta2), and anagen-prolonging insulin-like growth factor 1 (IGF-1) were evaluated by quantitative (immuno-) histomorphometry. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSK). RESULTS: Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine compared to male HFs. Caffeine counteracted testosterone-enhanced TGF-beta2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-beta2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSK, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, up-regulated IGF-1 gene expression and protein secretion, while TGF-beta2 protein secretion was down-regulated. CONCLUSIONS: This study reveals new growth-promoting effects of caffeine on human hair follicles of both genders at different (molecular, cellular and organ) levels. This article is protected by copyright. All rights reserved