Dietary Vitamin A Impacts Refractory Telogen

Area of Science:

• Dermatology and Hair Biology
• Molecular and Cellular Biology
• Nutritional Science

Background:

• Hair follicles (HF) undergo cyclical transitions: anagen (growth), catagen (regression), telogen (rest), and exogen (release).
• Telogen is subdivided into refractory and competent phases, distinguished by specific protein expressions like BMP4 and WNT7A.
• Refractory telogen is characterized by inhibited hair follicle stem cells (HFSC), and vitamin A metabolism is implicated in this process.

Purpose of the Study:

• To investigate the role of vitamin A metabolism in regulating hair follicle cycling, particularly during the refractory telogen phase.
• To clarify the conflicting results from previous studies on retinyl ester consumption and hair follicle arrest.
• To define the localization patterns of vitamin A metabolism proteins during different stages of telogen.

Main Methods:

• Utilized C57BL/6J mice fed varying levels of retinyl esters across two distinct studies with different dietary regimens and mouse ages.
• Assessed hair follicle cycling by examining the percentage of follicles in refractory telogen.
• Analyzed the expression of BMP4, WNT7A, Keratin 6 (KRT6), cellular retinoic acid binding protein 2 (CRABP2), and key retinoic acid (RA) metabolism enzymes (SDR16C5, ALDH1A2, CYP26B1).

Main Results:

• A higher percentage of hair follicles were found in refractory telogen under conditions of high retinyl ester intake (unpurified diet, excess intake from 12 weeks) and adequate intake (purified diet from 6 weeks).
• WNT7A expression correlated with these findings, supporting the classification of telogen stages.
• Localization studies revealed that KRT6 and CRABP2 were primarily in refractory telogen follicles in one study, but in both telogen types in the other.
• Key RA metabolism enzymes localized to BMP4-positive refractory telogen follicles in mice on an unpurified diet.

Conclusions:

• Vitamin A, particularly through retinoic acid (RA) metabolism, appears to contribute to the inhibition of hair follicle stem cells (HFSC) during refractory telogen.
• The effect of vitamin A on hair follicle cycling is likely dose-dependent and influenced by dietary composition and the age at which exposure begins.
• Further research is warranted to fully elucidate the mechanisms by which vitamin A regulates HFSC activity and hair follicle dormancy.