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Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, KoreaDepartment of Biomolecular Science, University of Science and Technology, Daejeon, Korea
Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, KoreaDepartment of Biomolecular Science, University of Science and Technology, Daejeon, Korea
Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, KoreaDepartment of Biomolecular Science, University of Science and Technology, Daejeon, Korea
The hair loss in male pattern baldness (MPB) is the result of miniaturization of the hair follicle and shortening of the anagen phase of the hair growth cycle mediated by dihydrotestosterone (DHT), which is metabolized from testosterone (T) and catalyzed by 5α-reductase (
), steroids extracted from the hair shaft were compared in balding and normal Korean and Caucasian subjects. Human hair fibers were obtained by cutting the proximal part hair from the vertex and occipital scalp, and the steroid levels were evaluated as described (Supplementary Information online, Materials and Methods). Subject consent for the study was not required because hair fiber is not considered to be human tissue by Korean law. All MPB patients were defined as having grade VI or greater disease using the Hamilton–Norwood Scale.
Of the 12 steroids studied, 9 steroids extracted from the vertex hair showed group differences (Table 1). The balding groups in both populations had significantly higher DHT levels (mean=6.48ngg−1 (P<0.0002) for Koreans and 4.59ngg−1 (P<0.004) for Caucasians) than the control groups (3.56ngg−1 for Koreans and 1.51ngg−1 for Caucasians). T levels were also increased in both balding groups (14.48ngg−1 (P<0.02) for Koreans and 5.87ngg−1 (P<0.02) for Caucasians) compared with their corresponding control groups. Balding Caucasians had 2-fold increased epitestosterone (Epi-T) levels compared with normal Caucasians (P<0.007), but only slight increases compared with normal Koreans, which might suggest different androgen metabolisms between the races. In addition, 5β-dihydroprogesterone (5β-DHP) levels were significantly increased in balding Koreans (P<0.0003) compared with normal Koreans, but were not significantly different from those in the Caucasian groups.
Table 1Steroid levels of the vertex hair shaft of balding and normal Korean and Caucasian subjects
Steroids extracted from 20mg of hair fiber were separated through an Ultra-1 capillary column (25m × 0.2mm i.d., 0.33-μm film thickness). The oven temperature was initially set to 215°C, ramped to 260°C at 1°Cminute−1 intervals, and then increased to 320°C (hold for 1min) using a 15°Cminute−1 ramping program. The carrier gas was ultra-high-purity helium at a column head pressure of 210.3kPa (column flow: 1.0mlminute−1 at an oven temperature of 215°C).
1 See “Materials and Methods” in the Supplementary Information online for the full names of the studied steroids.
2 Unpaired two-tailed Student’s t-test was used in group differences.
Between the different racial groups, both Korean groups had higher vertex androgen levels (>1.5-fold) than those of the Caucasian populations, with the exception of dehydroepiandrosterone (DHEA) (Table 1). The T concentrations were significantly higher in the Korean balding and normal groups (11.47ngg−1 (P<4 × 10−9) and 14.48ngg−1 (P<2 × 10−8), respectively) than in the corresponding Caucasian groups (3.57 and 5.87ngg−1). Epi-T levels were also higher in the Korean groups (28.15ngg−1 (P<0.001) for normal and 25.60ngg−1 (P<0.03) for balding subjects). The levels of the prohormone A-dione were also significantly higher (>2.5-fold) in the Korean groups than in the Caucasian groups (P<3 × 10−10 for balding and P<0.00001 for normal subjects). Levels of the biologically inactive steroid 11β-OH-An were also increased in the Korean populations (P<0.005 for normal and P<0.00001 for balding subjects). In addition, the levels of DHT (P<0.003) and 5α-dione (P<0.00001) were remarkably higher in the normal Koreans than in the normal Caucasians.
In contrast to the androgens, levels of pregnenolone, a DHEA, and A-dione precursor were markedly higher (>2.5-fold) in the Caucasian groups (64.56ngg−1 (P<0.0002) for balding and 61.03ngg−1 (P<0.0001) for normal subjects) than in the Korean groups (Figure 1). In particular, the 5β-DHP levels within the same racial groups were significantly altered along with the hair loss condition. In addition, the cholesterol levels of the normal Caucasian subjects were higher than those of the normal Korean subjects (P<0.0007).
Figure 1The altered steroid metabolism obtained from balding and normal Korean and Caucasian subjects. The line within the box represents the median, the lower boundary of the box indicates 25%, and the upper boundary of the box indicates 75%. Whiskers above and below indicate the maximum and minimum steroid levels, respectively. Dots above and below indicate the plot outliers with the 10th and 90th percentiles, respectively. BC, balding Caucasian; BK, balding Korean; DH, dihydrotestosterone; DHEA, dehydroepiandrosterone; 3β-HSD, 3β-hydroxysteroid dehydrogenase; 17α-HSD, 17α-hydroxysteroid dehydrogenase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; NC, normal Caucasian; NK, normal Korean.
The concentration ratio of the steroid metabolite and precursor, which could be used to derive insight into metabolic activity, was also evaluated (Supplementary Table S1 online). For 5α-reductase, the metabolic ratio of DHT/T was increased slightly in both balding populations. The activities of 3β-hydroxysteroid dehydrogenase (3β-HSD), which are represented by the DHEA to A-dione ratio, showed racial differences (P<0.005 for normal and P<0.006 for balding subjects).
The quantitative results obtained from the occipital hair were not consistent with those of the vertex hair (Supplementary Table S2 and S3 online). The occipital T levels were not significantly different between the Korean groups, a finding that is not concordant with that of an earlier report obtained from vertex hair (
). All vertex steroid levels except for 11β-OH-An tended to be slightly lower than occipital steroid levels in individual hairs. No significant differences between two sites were found in any case. This finding suggests that the distribution of androgens differs for each region of the scalp and may be useful for intersite comparison (
The differences in the metabolic ratio of DHT to T obtained from the vertex hair shafts were not statistically significant in any of the groups (Supplementary Table S1 online). An alternative metabolic ratio responsible for 5α-reductase activity with A-dione and T was therefore introduced because A-dione and T are reversibly catalyzed by 17β-HSD in the androgen metabolic process. Although these metabolic ratios tended to increase in both Caucasian groups, the differences were not statistically significant (Supplementary Table S1 online). In contrast to the 5α-reductase activity, the activity of 3β-HSD, which is indicated by the A-dione to DHEA metabolic ratio, was higher in the Korean groups. At the target cell levels, different androgenic productions could be regulated by the balance between 5α-reductase, 3β-HSD, and 17β-HSD (
Although our findings are based on the epithelial environments and not on the papilla cells, it confirms the existence of racial differences in hair steroid levels, and the results highlight the necessity for careful monitoring and controlling for multiple factors along with race before making a conclusion with result from the biological fluids. Further studies would need to compare the drug efficacies in the balding groups to provide a personalized and evidence-based approach to patient treatment.
ACKNOWLEDGMENTS
This study was supported by an intramural grant from the Korea Institute of Science and Technology and by the Converging Research Center Program through the Ministry of Education, Science and Technology (2011K000885).
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