Change in Hair Growth-related Gene Expression Profile in Human Isolated Hair Follicles Induced by 5-alpha Reductase Inhibitors, Dutasteride and Finasteride, in the Presence of Testosterone

Abstract

Objective: 5-α Reductase (5AR) subtypes I and II are suggested to be involved in the development of Andro-Genetic Alopecia (AGA); however, the involvement of type I 5AR in the pathogenesis of AGA and downstream molecular events following androgen receptor inhibition are still poorly understood. We investigated the changes in gene expression levels of growth factors and related molecules responsible for hair growth, such as enzymes and transcription factors, using the bulbar portions of plucked human hair follicles, and evaluated the involvement of type I 5AR in human hair growth. Methods: Anagen hairs were plucked from male donors with AGA and cultured in medium containing Di-Hydro Testosterone (DHT) or testosterone in the presence or absence of the 5AR inhibitors, dutasteride or finasteride. Total RNA extracted from the bulbar portions of hair follicles was subjected to quantitative reverse transcriptase polymerase chain reaction analysis to assess gene expression levels of growth factors and other related molecules. Results: DHT stimulation resulted in a trend to decrease the expression of genes encoding fibroblast growth factor 7 (FGF7; p=0.52), insulin-like growth factor 1 (IGF1; p=0.85) and WNT family member 5A (WNT5a; p=0.08). Subsequently, testosterone stimulation led to decreased expression of genes encoding FGF7 (p=0.53), IGF1 (p=0.93) and WNT5a (p=0.51), which was reversed by dutasteride or finasteride treatment. Conclusion: Among the assessed growth factors and other molecules related to hair growth, the expression levels of FGF7, IGF1 and WNT5a were reversed by 5AR inhibitors under testosterone stimulation. Our data suggest this assay may be useful to deeper dissect the effect of 5AR on human hair follicles and supports the previously unreported involvement of type I 5AR in hair growth.