- Email: [email protected]
Hair Steroid Profiling Reveals Racial Differences in Male Pattern Baldness between Korean and Caucasian Populations
LETTERS TO THE EDITOR
Hair Steroid Profiling Reveals Racial Differences in Male Pattern Baldness between Korean and Caucasian Populations Journal of Investigative Dermatology (2013) 133, 822–824; doi:10.1038/jid.2012.349; published online 15 November 2012
TO THE EDITOR 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 5a-reductase (Itami et al., 1994; Sinclair, 1998). However, the androgen activities in MPB within different racial groups are not completely understood (Santner et al., 1998).
As biological fluids demonstrate no correlation between androgen levels and MPB (Phillipou and Kirk, 1981), 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 ¼ 6.48 ng g 1 (Po0.0002) for Koreans and 4.59 ng g 1 (Po0.004) for Caucasians) than the control groups (3.56 ng g 1
Table 1. Steroid levels of the vertex hair shaft of balding and normal Korean and Caucasian subjects Concentration (ng g 1) Compound1 DHT
NK 3.56±1.51
BK
NC
6.48±2.31
1.51±1.26
P-value2 BC 4.59±3.25
NK versus BK
NC versus BC
NK versus NC
BK versus BC
o0.0002
o0.004
o0.003
NS3
3.91±1.86
4.65±2.03
4.03±2.31
7.01±7.42
NS
NS
NS
NS
T
11.47±3.36
14.48±3.21
3.57±1.94
5.87±2.77
o0.02
o0.02
o4 10-9
o2 10-8
Epi-T
28.15±18.45
25.60±12.17
10.46±6.01
17.68±6.73
NS
o0.007
o0.001
o0.03
A-dione
12.46±3.02
11.52±4.74
4.24±1.15
4.75±1.85
NS
NS
o3 10-10
o0.0001
11b-OH-An
20.25±9.04
26.19±12.04
12.35±5.74
10.01±6.53
NS
NS
o0.005
o0.0001
4.07±1.88
3.96±1.67
1.30±0.94
2.45±1.77
NS
NS
o0.00001
NS
26.20±20.49
24.13±10.07
61.03±19.64
64.56±28.82
NS
NS
o0.0001
o0.0002
20.16 ±11.12
187.34±99.60
54.29±41.14
39.34±45.35
o0.0003
NS
NS
o0.0006
Pregnanolone
85.84±47.37
105.84±38.14
63.60±35.36
78.12±43.58
NS
NS
NS
NS
Pregnanetriol
9.72±4.61
9.70±3.93
8.08±3.11
11.13±5.93
NS
NS
NS
NS
1,907.83±586.65
NS
NS
o0.0007
NS
DHEA
5a-dione Preg 5b-DHP
Cholesterol
1,656.04±389.34
1,891.82±508.89
2,285.19±522.18
Abbreviations: BC, balding Caucasian; BK, balding Korean; DHEA, dehydroepiandrosterone; DHP, dihydroprogesterone; DHT, dihydrotestosterone; Epi-T, epitestosterone; NC, normal Caucasian; NK, normal Korean. Steroids extracted from 20 mg of hair fiber were separated through an Ultra-1 capillary column (25 m 0.2 mm i.d., 0.33-mm film thickness). The oven temperature was initially set to 215˚ C, ramped to 260˚ C at 1˚ C minute 1 intervals, and then increased to 320˚ C (hold for 1 min) using a 15˚ C minute 1 ramping program. The carrier gas was ultra-high-purity helium at a column head pressure of 210.3 kPa (column flow: 1.0 ml minute 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. 3 Not statistically significant.
Abbreviations: DHEA, dehydroepiandrosterone; 5b-DHP, 5b-dihydroprogesterone; DHT, dihydrotestosterone; 3b-HSD, 3b-hydroxysteroid dehydrogenase; 17b-HSD, 17b-hydroxysteroid dehydrogenase; GC–MS, gas chromatography–mass spectrometry; MPB, male pattern baldness; T, testosterone
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MH Choi et al. Racial Differences in Male Pattern Baldness
3,500 3,000 2,500 2,000 1,500 1,000 500
HO
O
HO
70 60 OH 50 40 30 20 10 0
HO
H
50 O 40 30 20 10 0
11β-Hydroxyandrosterone
Epitestosterone
Cholesterol
17α-HSD 140 O 120 100 80 60 40 20 0
HO
O
7α-Hydroxylase/ 17,20-Lyase 1
2
3
HO
4
Pregnenolone
30 25 20 15 10 5 0
O
3β-HSD
O
25 20 15 10 5 0
DHEA
O
O
H
5β-Dihydroprogesterone
O
10 8 6 4 2 0
H
5α-Androstanedione
17β-HSD
OH
400 300 200 100 0
5α-Reductase
Androstenedione
(Progesterone)
O
O
25 20 15 10 5 0
Testosterone
17β-HSD
5α-Reductase
O
OH 12 10 8 6 4 2 0
DHT
3α-HSD O
HO
H
200 180 160 140 120 100 80 60 40 20 0
NK BK NC
Pregnanolone HO
HO
H
BC
22 20 OH 18 16 14 12 10 8 6 4 2
Pregnanetriol
Figure 1. The 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; 3b-HSD, 3b-hydroxysteroid dehydrogenase; 17a-HSD, 17a-hydroxysteroid dehydrogenase; 17b-HSD, 17b-hydroxysteroid dehydrogenase; NC, normal Caucasian; NK, normal Korean.
for Koreans and 1.51 ng g 1 for Caucasians). T levels were also increased in both balding groups (14.48 ng g 1 (Po0.02) for Koreans and 5.87 ng g 1 (Po0.02) for Caucasians) compared with their corresponding control groups. Balding Caucasians had 2-fold increased epitestosterone (Epi-T) levels compared with normal Caucasians (Po0.007), but only slight increases compared with normal Koreans, which might suggest different androgen metabolisms between the races. In addition, 5b-dihydroprogesterone (5bDHP) levels were significantly increased in balding Koreans (Po0.0003) compared with normal Koreans, but were not significantly different from those in the Caucasian groups. Between the different racial groups, both Korean groups had higher vertex androgen levels (41.5-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 (11.47 ng g 1 (Po4 10 9) and 14.48 ng g 1 (Po2 10 8), respectively) than in the corresponding Caucasian groups (3.57 and 5.87 ng g 1). Epi-T levels were also higher in the Korean groups (28.15 ng g 1 (Po0.001) for normal and 25.60 ng g 1 (Po0.03) for balding subjects). The levels of the prohormone A-dione were also significantly higher (42.5-fold) in the Korean groups than in the Caucasian groups (Po3 10 10 for balding and Po0.00001 for normal subjects). Levels of the biologically inactive steroid 11bOH-An were also increased in the Korean populations (Po0.005 for normal and Po0.00001 for balding subjects). In addition, the levels of DHT (Po0.003) and 5adione (Po0.00001) 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 (42.5-fold) in the Caucasian groups (64.56 ng g 1 (Po0.0002) for balding and 61.03 ng g 1 (Po0.0001) for normal subjects) than in the Korean groups (Figure 1). In particular, the 5b-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 (Po0.0007). 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 5a-reductase, the metabolic ratio of DHT/T was increased slightly in both balding populations. The activities of 3b-hydroxysteroid dehydrogenase (3b-HSD), which are represented by the DHEA to A-dione ratio, showed racial differences (Po0.005 for normal and Po0.006 for balding subjects). www.jidonline.org
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BK Sun et al. RAS Mutations in Nevus Sebaceus
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 (Choi et al., 2001). In addition, the DHT/T ratio, one of the indicators of MPB (Choi et al., 2001; Bang et al., 2004), was lower in the vertex hair after treatment with 5areductase inhibitors, both finasteride and dutasteride, but not in the occipital hair (Ryu et al., 2006; Jung et al., 2011). All vertex steroid levels except for 11b-OHAn 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 (Rushton et al., 1991). 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 5a-reductase activity with A-dione and T was therefore introduced because A-dione and T are reversibly catalyzed by 17b-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
5a-reductase activity, the activity of 3bHSD, 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 5a-reductase, 3b-HSD, and 17b-HSD (Eicheler et al., 1998). 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 evidencebased approach to patient treatment. CONFLICT OF INTEREST The authors state no conflict of interest.
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).
Man Ho Choi1,2, Sun Ju Kim1,2, Bark-Lynn Lew3, Woo Young Sim3 and Bong Chul Chung1,2 1
Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, Korea; 2Department of Biomolecular Science, University of Science and Technology, Daejeon, Korea and 3Department of Dermatology, Kyung Hee University, Seoul, Korea E-mail: [email protected]
SUPPLEMENTARY MATERIAL Supplementary material is linked to the online version of the paper at http://www.nature.com/jid
REFERENCES Bang HJ, Yang YJ, Lho DS et al. (2004) Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness. J Dermatol Sci 34:11–6 Choi MH, Yoo YS, Chung BC (2001) Biochemical roles of testosterone and epitestosterone to 5 alpha-reductase as indicators of male-pattern baldness. J Invest Dermatol 116:57–61 Eicheler W, Happle R, Hoffmann R (1998) 5 alphareductase activity in the human hair follicle concentrates in the dermal papilla. Arch Dermatol Res 290:126–32 Itami S, Sonoda T, Kurata S et al. (1994) Mechanism of action of androgen in hair follicles J Dermatol Sci 7:S98–103 Jung HJ, Kim SJ, Lee YW et al. (2011) Gas chromatography/mass spectrometry based hair steroid profiling may reveal pathogenesis in hair follicles of the scalp. Rapid Commun Mass Spectrom 25:1184–92 Phillipou G, Kirk J (1981) Significance of steroid measurements in male pattern alopecia. Clin Exp Dermatol 6:53–6 Rushton DH, Ramsat ID, Norris MJ et al. (1991) Natural progression of male pattern baldness in young men. Clin Exp Dermatol 16:188–92 Ryu HK, Kim KM, Yoo EA et al. (2006) Evaluation of androgens in the scalp hair and plasma of patients with male-pattern baldness before and after finasteride administration. Br J Dermatol 154:730–4 Santner SJ, Albertson B, Zhang GY et al. (1998) Comparative rates of androgen production and metabolism in Caucasian and Chinese subjects. J Clin Endocrinol Metab 83: 2104–9 Sinclair R (1998) Male pattern androgenetic alopecia. Br Med J 317:86–9
See related commentary on pg 597
Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome Journal of Investigative Dermatology (2013) 133, 824–827; doi:10.1038/jid.2012.377; published online 25 October 2012
TO THE EDITOR Nevus sebaceus is a common congenital skin hamartoma, classically appearing as a yellow-hued plaque on the scalp, face, or neck. It is the hallmark lesion of Schimmelpenning/nevus seba-
ceus syndrome (OMIM: 163200), a multisystem disorder that includes a spectrum of central nervous system, ocular, skeletal, and cardiovascular defects. Secondary neoplasms arise within nevus sebaceus at a modest but elevated
Abbreviations: MAPK, mitogen-activated protein kinase; pERK, phosphorylated ERK
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Journal of Investigative Dermatology (2013), Volume 133
rate (Moody et al., 2012), prompting disagreement about whether they should be routinely excised (Shwayder, 2011). Determining the pathogenesis of nevus sebaceus would provide a framework to better understand this lesion and its associated syndrome. The appearance of nevus sebaceus along Blaschko’s lines suggests that a
Copyright of Journal of Investigative Dermatology is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Hair Steroid Profiling Reveals Racial Differences in Male Pattern Baldness between Korean and Caucasian Populations Journal of Investigative Dermatology (2013) 133, 822–824; doi:10.1038/jid.2012.349; published online 15 November 2012
TO THE EDITOR 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 5a-reductase (Itami et al., 1994; Sinclair, 1998). However, the androgen activities in MPB within different racial groups are not completely understood (Santner et al., 1998).
As biological fluids demonstrate no correlation between androgen levels and MPB (Phillipou and Kirk, 1981), 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 ¼ 6.48 ng g 1 (Po0.0002) for Koreans and 4.59 ng g 1 (Po0.004) for Caucasians) than the control groups (3.56 ng g 1
Table 1. Steroid levels of the vertex hair shaft of balding and normal Korean and Caucasian subjects Concentration (ng g 1) Compound1 DHT
NK 3.56±1.51
BK
NC
6.48±2.31
1.51±1.26
P-value2 BC 4.59±3.25
NK versus BK
NC versus BC
NK versus NC
BK versus BC
o0.0002
o0.004
o0.003
NS3
3.91±1.86
4.65±2.03
4.03±2.31
7.01±7.42
NS
NS
NS
NS
T
11.47±3.36
14.48±3.21
3.57±1.94
5.87±2.77
o0.02
o0.02
o4 10-9
o2 10-8
Epi-T
28.15±18.45
25.60±12.17
10.46±6.01
17.68±6.73
NS
o0.007
o0.001
o0.03
A-dione
12.46±3.02
11.52±4.74
4.24±1.15
4.75±1.85
NS
NS
o3 10-10
o0.0001
11b-OH-An
20.25±9.04
26.19±12.04
12.35±5.74
10.01±6.53
NS
NS
o0.005
o0.0001
4.07±1.88
3.96±1.67
1.30±0.94
2.45±1.77
NS
NS
o0.00001
NS
26.20±20.49
24.13±10.07
61.03±19.64
64.56±28.82
NS
NS
o0.0001
o0.0002
20.16 ±11.12
187.34±99.60
54.29±41.14
39.34±45.35
o0.0003
NS
NS
o0.0006
Pregnanolone
85.84±47.37
105.84±38.14
63.60±35.36
78.12±43.58
NS
NS
NS
NS
Pregnanetriol
9.72±4.61
9.70±3.93
8.08±3.11
11.13±5.93
NS
NS
NS
NS
1,907.83±586.65
NS
NS
o0.0007
NS
DHEA
5a-dione Preg 5b-DHP
Cholesterol
1,656.04±389.34
1,891.82±508.89
2,285.19±522.18
Abbreviations: BC, balding Caucasian; BK, balding Korean; DHEA, dehydroepiandrosterone; DHP, dihydroprogesterone; DHT, dihydrotestosterone; Epi-T, epitestosterone; NC, normal Caucasian; NK, normal Korean. Steroids extracted from 20 mg of hair fiber were separated through an Ultra-1 capillary column (25 m 0.2 mm i.d., 0.33-mm film thickness). The oven temperature was initially set to 215˚ C, ramped to 260˚ C at 1˚ C minute 1 intervals, and then increased to 320˚ C (hold for 1 min) using a 15˚ C minute 1 ramping program. The carrier gas was ultra-high-purity helium at a column head pressure of 210.3 kPa (column flow: 1.0 ml minute 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. 3 Not statistically significant.
Abbreviations: DHEA, dehydroepiandrosterone; 5b-DHP, 5b-dihydroprogesterone; DHT, dihydrotestosterone; 3b-HSD, 3b-hydroxysteroid dehydrogenase; 17b-HSD, 17b-hydroxysteroid dehydrogenase; GC–MS, gas chromatography–mass spectrometry; MPB, male pattern baldness; T, testosterone
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MH Choi et al. Racial Differences in Male Pattern Baldness
3,500 3,000 2,500 2,000 1,500 1,000 500
HO
O
HO
70 60 OH 50 40 30 20 10 0
HO
H
50 O 40 30 20 10 0
11β-Hydroxyandrosterone
Epitestosterone
Cholesterol
17α-HSD 140 O 120 100 80 60 40 20 0
HO
O
7α-Hydroxylase/ 17,20-Lyase 1
2
3
HO
4
Pregnenolone
30 25 20 15 10 5 0
O
3β-HSD
O
25 20 15 10 5 0
DHEA
O
O
H
5β-Dihydroprogesterone
O
10 8 6 4 2 0
H
5α-Androstanedione
17β-HSD
OH
400 300 200 100 0
5α-Reductase
Androstenedione
(Progesterone)
O
O
25 20 15 10 5 0
Testosterone
17β-HSD
5α-Reductase
O
OH 12 10 8 6 4 2 0
DHT
3α-HSD O
HO
H
200 180 160 140 120 100 80 60 40 20 0
NK BK NC
Pregnanolone HO
HO
H
BC
22 20 OH 18 16 14 12 10 8 6 4 2
Pregnanetriol
Figure 1. The 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; 3b-HSD, 3b-hydroxysteroid dehydrogenase; 17a-HSD, 17a-hydroxysteroid dehydrogenase; 17b-HSD, 17b-hydroxysteroid dehydrogenase; NC, normal Caucasian; NK, normal Korean.
for Koreans and 1.51 ng g 1 for Caucasians). T levels were also increased in both balding groups (14.48 ng g 1 (Po0.02) for Koreans and 5.87 ng g 1 (Po0.02) for Caucasians) compared with their corresponding control groups. Balding Caucasians had 2-fold increased epitestosterone (Epi-T) levels compared with normal Caucasians (Po0.007), but only slight increases compared with normal Koreans, which might suggest different androgen metabolisms between the races. In addition, 5b-dihydroprogesterone (5bDHP) levels were significantly increased in balding Koreans (Po0.0003) compared with normal Koreans, but were not significantly different from those in the Caucasian groups. Between the different racial groups, both Korean groups had higher vertex androgen levels (41.5-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 (11.47 ng g 1 (Po4 10 9) and 14.48 ng g 1 (Po2 10 8), respectively) than in the corresponding Caucasian groups (3.57 and 5.87 ng g 1). Epi-T levels were also higher in the Korean groups (28.15 ng g 1 (Po0.001) for normal and 25.60 ng g 1 (Po0.03) for balding subjects). The levels of the prohormone A-dione were also significantly higher (42.5-fold) in the Korean groups than in the Caucasian groups (Po3 10 10 for balding and Po0.00001 for normal subjects). Levels of the biologically inactive steroid 11bOH-An were also increased in the Korean populations (Po0.005 for normal and Po0.00001 for balding subjects). In addition, the levels of DHT (Po0.003) and 5adione (Po0.00001) 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 (42.5-fold) in the Caucasian groups (64.56 ng g 1 (Po0.0002) for balding and 61.03 ng g 1 (Po0.0001) for normal subjects) than in the Korean groups (Figure 1). In particular, the 5b-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 (Po0.0007). 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 5a-reductase, the metabolic ratio of DHT/T was increased slightly in both balding populations. The activities of 3b-hydroxysteroid dehydrogenase (3b-HSD), which are represented by the DHEA to A-dione ratio, showed racial differences (Po0.005 for normal and Po0.006 for balding subjects). www.jidonline.org
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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 (Choi et al., 2001). In addition, the DHT/T ratio, one of the indicators of MPB (Choi et al., 2001; Bang et al., 2004), was lower in the vertex hair after treatment with 5areductase inhibitors, both finasteride and dutasteride, but not in the occipital hair (Ryu et al., 2006; Jung et al., 2011). All vertex steroid levels except for 11b-OHAn 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 (Rushton et al., 1991). 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 5a-reductase activity with A-dione and T was therefore introduced because A-dione and T are reversibly catalyzed by 17b-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
5a-reductase activity, the activity of 3bHSD, 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 5a-reductase, 3b-HSD, and 17b-HSD (Eicheler et al., 1998). 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 evidencebased approach to patient treatment. CONFLICT OF INTEREST The authors state no conflict of interest.
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).
Man Ho Choi1,2, Sun Ju Kim1,2, Bark-Lynn Lew3, Woo Young Sim3 and Bong Chul Chung1,2 1
Future Convergence Research Division, Korea Institute of Science and Technology, Seoul, Korea; 2Department of Biomolecular Science, University of Science and Technology, Daejeon, Korea and 3Department of Dermatology, Kyung Hee University, Seoul, Korea E-mail: [email protected]
SUPPLEMENTARY MATERIAL Supplementary material is linked to the online version of the paper at http://www.nature.com/jid
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See related commentary on pg 597
Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome Journal of Investigative Dermatology (2013) 133, 824–827; doi:10.1038/jid.2012.377; published online 25 October 2012
TO THE EDITOR Nevus sebaceus is a common congenital skin hamartoma, classically appearing as a yellow-hued plaque on the scalp, face, or neck. It is the hallmark lesion of Schimmelpenning/nevus seba-
ceus syndrome (OMIM: 163200), a multisystem disorder that includes a spectrum of central nervous system, ocular, skeletal, and cardiovascular defects. Secondary neoplasms arise within nevus sebaceus at a modest but elevated
Abbreviations: MAPK, mitogen-activated protein kinase; pERK, phosphorylated ERK
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rate (Moody et al., 2012), prompting disagreement about whether they should be routinely excised (Shwayder, 2011). Determining the pathogenesis of nevus sebaceus would provide a framework to better understand this lesion and its associated syndrome. The appearance of nevus sebaceus along Blaschko’s lines suggests that a
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