mRNA Levels of Aromatase, 5α-Reductase Isozymes, and Prostate Cancer-Related Genes in Plucked Hair from Young Men with Androgenic Alopecia

Abstract

Androgenic alopecia (AGA) is the most prevalent type of progressive hair loss and has psychological repercussions. Nevertheless, the effectiveness of current pharmacological treatments remains limited, in part because the molecular basis of the disease has not been fully elucidated. Our group previously highlighted the important roles of aromatase and 5α-reductase (5α-R) in alopecia in young women with female pattern hair loss. Additionally, an association has been proposed between AGA and prostate cancer (PCa), suggesting that genes implicated in PCa would also be involved in AGA. A low-invasive, sensitive, and precise method was used to determine mRNA levels of aromatase, 5α-R isozymes, and 84 PCa-related genes in samples of plucked hair from young men with AGA and controls. Samples were obtained with a trichogram from the vertex scalp, and mRNA levels were quantified using real-time RT-PCR. The men with AGA had significantly higher 5α-R2 mRNA levels in comparison to controls; interestingly, some of them also showed markedly elevated mRNA levels of 5α-R1 or 5α-R3 or of both, which may explain the varied response to 5α-R inhibitor treatments. The men with AGA also showed significant changes versus controls in 6 out of the 84 genes implicated in PCa. This study contributes greater knowledge of the molecular bases of AGA, facilitating early selection of the most appropriate pharmacological therapy and opening the way to novel treatments.

Keywords: 5α-R isozymes; androgenic alopecia; aromatase; prostate cancer genes; trichogram.

Figure 1

mRNA levels of 5α-Reductase type 1 (5α-R1) (A), 5α-Reductase type 2 (5α-R2) (B), 5α-Reductase type 3 (5α-R3) (C), and aromatase (D) in anagen hairs plucked from young men with AGA (n = 10) and controls (healthy men with no hair loss or thinning) (n = 10). The 5α-R2 mRNA levels were significantly higher in the AGA group than in controls (p = 0.0015). Data are expressed as means ± SD.

Figure 2

PCR-array analysis showing the quantification of mRNA levels of 84 genes implicated in prostate cancer in plucked hair from young men with AGA and controls. (A) Cluster analysis. The color intensity from green to red shows the degree of downregulation (green) to upregulation (red) compared with the other samples. A group of three control cases is clustered on the right side, and a group of three young men with AGA cases is clustered on the left side. (B) Volcano plot showing gene expression differences between young men with AGA and control groups by plotting the log₂ of fold changes in gene expression on the x-axis against their statistical significance on the y-axis. Each spot represents a single gene. The left vertical axis indicates a two-fold lower expression in young men with AGA versus the control group (blue spots); the central vertical axis shows no change in gene expression; and the right vertical axis indicates a two-fold higher expression in young men with AGA versus controls (yellow spots). The blue line indicates the t-test threshold (p < 0.05). Statistically significant upregulations/downregulations of genes are indicated by the gene symbols FOXO1 (Forkhead box O1), GPX3 (glutathione peroxidase 3 (plasma)), IL6 (interleukin 6 (interferon, beta 2)), AR (androgen receptor), APC (adenomatous polyposis coli), and ETV1 (Ets variant 1). Three independent experiments were performed.