Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and transforming growth factor-β2/insulin-like growth factor-1-mediated regulation of the hair cycle in male and female human hair follicles in vitro

• Published in: British journal of dermatology (1951) Vol. 171; no. 5; pp. 1031 - 1043
• Main Authors: Fischer, T.W., Herczeg-Lisztes, E., Funk, W., Zillikens, D., Bíró, T., Paus, R.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.11.2014; Wiley-Blackwell; Oxford University Press
• Subjects: Androgens - pharmacology; Antigens - metabolism; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caffeine; Caffeine - pharmacology; Cell culture; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Dermatology; Elongation; Female; Follicles; Gene expression; Growth factors; Hair; Hair - drug effects; Hair - growth & development; Hair Follicle - drug effects; Histomorphometry; Humans; In Vitro Techniques; Insulin; Insulin-Like Growth Factor I - drug effects; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - secretion; Insulin-like growth factors; Intermediate Filament Proteins - metabolism; Keratinocytes; Keratinocytes - drug effects; Male; Medical sciences; Organ culture; Phosphodiesterase Inhibitors - pharmacology; Protein expression; Proteins; Scalp; Testosterone; Testosterone - pharmacology; Transforming Growth Factor beta2 - drug effects; Transforming Growth Factor beta2 - metabolism; Transforming Growth Factor beta2 - secretion; Human; Cell proliferation; Hair; Root; CNS stimulant; Dermatology; Psychotropic; Hair follicle; Male; Outer; Keratinocyte growth factor; Proliferation; Insulin like growth factor 1; In vitro; Cycle; Sheath; Respiratory analeptic; Hair (head); Regulation(control); Transforming growth factor β2; Female; Caffeine
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.13114

Summary Background Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ‐cultured male human hair follicles (HFs). Objectives We aimed to investigate the impact of caffeine (i) on additional key hair growth parameters, (ii) on major hair growth regulatory factors and (iii) on male vs. 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 μg mL−1) or in combination with caffeine (0·005–0·0005%). The following effects on hair shaft elongation were evaluated by quantitative (immuno)histomorphometry: HF cycling (anagen–catagen transition); hair matrix keratinocyte proliferation; expression of a key catagen inducer, transforming growth factor (TGF)‐β2; and expression of the anagen‐prolonging insulin‐like growth factor (IGF)‐1. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSKs). Results Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine than male HFs. Caffeine counteracted testosterone‐enhanced TGF‐β2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF‐β2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF‐1 protein expression. In ORSKs, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, and upregulated IGF‐1 gene expression and protein secretion, while TGF‐β2 protein secretion was downregulated. Conclusions This study reveals new growth‐promoting effects of caffeine on human hair follicles in subjects of both sexes at different levels (molecular, cellular and organ). What's already known about this topic? Caffeine stimulates hair growth in androgen‐sensitive testosterone‐suppressed male human hair follicles (HFs) in vitro. What does this study add? The first evidence is presented for caffeine‐stimulated growth of female human HFs, which are more caffeine sensitive than male HFs. Proliferation is increased by caffeine in human HF matrix keratinocytes in situ and in HF‐derived outer root sheath keratinocytes (ORSKs). The catagen inducer transforming growth factor‐β2 is downregulated, and the anagen‐promoting factor insulin‐like growth factor‐1 is upregulated in human HFs in situ and in ORSKs.