Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Archives of Dermatological Research
Published in: Archives of Dermatological Research 1/2018

01-01-2018 | Original Paper

5α-Reductase isozymes and aromatase mRNA levels in plucked hair from young women with female pattern hair loss

Authors: P. Sánchez, C. Serrano-Falcón, J. M. Torres, S. Serrano, E. Ortega

Published in: Archives of Dermatological Research | Issue 1/2018

Login to get access

Abstract

Female pattern hair loss (FPHL) is an important hair disorder, especially when young women are affected. However, pharmacological treatments are not successful in all women. Androgens, especially dihydrotestosterone (DHT), may play a role in FPHL, but many women with this disorder have normal serum androgen levels. It therefore appears that hair follicle levels of DHT depend on in situ testosterone (T) metabolism. Because T can be converted to DHT or estradiol (E2) by 5α-reductase (5α-R) and aromatase, respectively, these enzymes would determine DHT and E2 concentrations and their ratio. We propose and apply a low-invasive, sensitive and precise method for the absolute quantification of mRNA levels of aromatase and 5α-R isozymes (type 1, type 2 and type 3) in plucked hair from young women with FPHL. Normoandrogenic women with FPHL and controls were studied. Plucked hair samples were obtained by trichogram from vertex scalp and mRNA levels quantified by real-time RT-PCR. We revealed for the first time the presence of 5α-R3 mRNA in human hair. Interestingly, one, two, or even three 5α-R isozymes were increased in some women with FPHL but not in others, which may explain the lack of response to 5α-R inhibitors in some FPHL cases. Aromatase mRNA levels were significantly lower in women with FPHL than in controls. It may therefore produce a reduction in oestrogen levels and an increase in the androgen/oestrogen ratio in hair. The proposed low-invasive technique offers a molecular aetiologic diagnosis of FPHL for the selection of more appropriate pharmacological treatments with early predicted effectiveness.
Literature
1.
Atanaskova Mesinkovska N, Bergfeld WF (2013) Hair: what is new in diagnosis and management? Female pattern hair loss update: diagnosis and treatment. Dermatol Clin 31:119–127CrossRefPubMed
2.
Azzouni F, Godoy A, Li Y, Mohler J (2012) The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol 2012:530121
3.
Bayne EK, Flanagan J, Einstein M, Ayala J, Chang B, Azzolina B, Whiting DA, Mumford RA, Thiboutot D, Singer II, Harris G (1999) Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp. Br J Dermatol 141:481–491CrossRefPubMed
4.
Castro B, Sánchez P, Torres JM, Preda O, del Moral RG, Ortega E (2013) Bisphenol A exposure during adulthood alters expression of aromatase and 5α-reductase isozymes in rat prostate. PLoS One 8:e55905CrossRefPubMedPubMedCentral
5.
6.
Cousen P, Messenger A (2010) Female pattern hair loss in complete androgen insensitivity syndrome. Br J Dermatol 162:1135–1137CrossRefPubMed
7.
Eicheler W, Happle R, Hoffmann R (1998) 5 alpha-reductase activity in the human hair follicle concentrates in the dermal papilla. Arch Dermatol Res 290:126–132CrossRefPubMed
8.
Eicheler W, Tuohimaa P, Vilja P, Adermann K, Forssmann WG, Aumüller G (1994) Immunocytochemical localization of human 5 alpha-reductase 2 with polyclonal antibodies in androgen target and non-target human tissues. J Histochem Cytochem 42:667–675CrossRefPubMed
9.
Ellis JA, Sinclair R, Harrap SB (2002) Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med 4:1–11CrossRef
10.
Fronhoffs S, Totzke G, Stier S, Wernert N, Rothe M, Brüning T, Koch B, Sachinidis A, Vetter H, Ko Y (2002) A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction. Mol Cell Probes 16:99–110CrossRefPubMed
11.
Gerst C, Dalko M, Pichaud P, Galey JB, Buan B, Bernard BA (2002) Type-1 steroid 5 alpha-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5 alpha-reductase. Exp Dermatol 11:52–58CrossRefPubMed
12.
13.
14.
Hoffmann R (2003) Steroidogenic isoenzymes in human hair and their potential role in androgenetic alopecia. Dermatology 206:85–95CrossRefPubMed
15.
Hoffmann R, Happle R (1999) Finasteride is the main inhibitor of 5α-reductase activity in microdissected dermal papillae of human hair follicles. Arch Dermatol Res 29:100–103CrossRef
16.
Hoffmann R, Niiyama S, Huth A, Kissling S, Happle R (2002) 17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo. Exp Dermatol 11:376–380CrossRefPubMed
17.
Imperato-McGinley J, Peterson RE, Gautier T, Cooper G, Danner R, Arthur A, Morris PL, Sweeney WJ, Shackleton C (1982) Hormonal evaluation of a large kindred with complete androgen insensitivity: evidence for secondary 5 alpha-reductase deficiency. J Clin Endocrinol Metab 54:931–941CrossRefPubMed
18.
Inui S, Itami S (2013) Androgen actions on the human hair follicle: perspectives. Exp Dermatol 22:168–171CrossRefPubMed
19.
Inui S, Itami S (2011) Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla. J Dermatol Sci 61:1–6CrossRefPubMed
20.
Jung HJ, Kim SJ, Lee WY, Chung BC, Choi MH (2011) Gas chromatography/mass spectrometry based hair steroid profiling may reveal pathogenesis in hair follicles of the scalp. Rapid Commun Mass Spectrom 25:1184–1192CrossRefPubMed
21.
Kanda N, Watanabe S (2002) 17beta-estradiol enhances vascular endothelial growth factor production and dihydrotestosterone antagonizes the enhancement via the regulation of adenylate cyclase in differentiated THP-1 cells. J Invest Dermatol 118:519–529CrossRefPubMed
22.
Kang JI, Kim SC, Kim MK, Boo HJ, Kim EJ, Im GJ, Kim YH, Hyun JW, Kang JH, Koh YS, Park DB, Yoo ES, Kang HK (2015) Effects of dihydrotestosterone on rat dermal papilla cells in vitro. Eur J Pharmacol 757:74–83CrossRefPubMed
23.
Kanti V, Nuwayhid R, Lindner J, Hillmann K, Stroux A, Bangemann N, Kleine-Tebbe A, Blume-Peytavi U, Garcia Bartels N (2014) Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol 170:643–650
24.
25.
Kim MS, Chae HJ, Shin TY, Kim HM, Kim HR (2001) Estrogen regulates cytokine release in human mast cells. Immunopharmacol Immunotoxicol 23:495–504CrossRefPubMed
26.
Langan EA, Paus R (2010) Female pattern hair loss: beyond an androgenic aetiology? Br J Dermatol 163:1140–1141CrossRefPubMed
27.
28.
29.
Matsuda T, Yamamoto T, Muraguchi A, Saatcioglu F (2001) Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3. J Biol Chem 276:42908–42914CrossRefPubMed
30.
Ohnemus U, Uenalan M, Inzunza J, Gustafsson JA, Paus R (2006) The hair follicle as an estrogen target and source. Endocr Rev 27:677–706CrossRefPubMed
31.
Oliveira IO, Lhullier C, Brum IS, Spritzer PM (2003) The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals. Braz J Med Biol Res 36:1447–1454CrossRefPubMed
32.
Orme S, Cullen DR, Messenger AG (1999) Diffuse female hair loss: are androgens necessary? Br J Dermatol 141:521–523CrossRefPubMed
33.
Ozdemir S, Ozdemir M, Görkemli H, Kiyici A, Bodur S (2010) Specific dermatologic features of the polycystic ovary syndrome and its association with biochemical markers of the metabolic syndrome and hyperandrogenism. Acta Obstet Gynecol Scand 89:199–204CrossRefPubMed
34.
Pfaffl MW, Hageleit M (2001) Validities of mRNA quantification using recombinant RNA and recombinant DNA external calibration curves in real-time RT-PCR. Biotech Lett 23:275–282CrossRef
35.
Philpott MP, Sanders DA, Kealey T (1994) Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro. J Invest Dermatol 102:857–861CrossRefPubMed
36.
Poletti A, Celotti F, Motta M, Martini L (1996) Characterization of rat 5alpha-reductases type 1 and type 2 expressed in Saccharomyces cerevisiae. Biochem J 314:1047–1052CrossRefPubMedPubMedCentral
37.
Quinn M, Shinkai K, Pasch L, Kuzmich L, Cedars M, Huddleston H (2014) Prevalence of androgenic alopecia in patients with polycystic ovary syndrome and characterization of associated clinical and biochemical features. Fertil Steril 101:1129–1134CrossRefPubMed
38.
39.
Rasmussen R (2001) Quantification on the LightCycler. In: Meuer S, Wittwer C, Nakagawara K (eds) Rapid cycle real-time PCR, methods and applications. Springer, Heidelberg, pp 21–34CrossRef
40.
Richeti F, Kochi C, Rocha MN, Sant’Anna Corrêa C, Lazzarini R, Guazzelli RM, Mendonça RF, Melo MR, Longui CA (2013) Increased androgen receptor messenger RNA in frontal-parietal hair follicles of women with androgenetic alopecia. Genet Mol Res 12:1834–1840CrossRefPubMed
41.
Sawaya ME, Penneys NS (1992) Immunohistochemical distribution of aromatase and 3B-hydroxysteroid dehydrogenase in human hair follicle and sebaceous gland. J Cutan Pathol 19:309–314CrossRefPubMed
42.
Sawaya ME, Price VH (1997) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol 109:296–300CrossRefPubMed
43.
Seale LR, Eglini AN, McMichael AJ (2016) Side effects related to 5 α-reductase inhibitor treatment of hair loss in women: a review. J Drugs Dermatol 15:414–419PubMed
44.
Serrano-Falcón C, Fernández-Pugnaire MA, Serrano-Ortega S (2013) Hair and scalp evaluation: the trichogram. Actas Dermosifiliogr 104:867–876CrossRefPubMed
45.
46.
Torres JM, Ruiz E, Ortega E (2003) Development of a quantitative RT-PCR method to study 5alpha-reductase mRNA isozymes in rat prostate in different androgen status. Prostate 56:74–79CrossRefPubMed
47.
Tsuji Y, Denda S, Soma T, Raftery L, Momoi T, Hibino T (2003) A potential suppressor of TGF-beta delays catagen progression in hair follicles. J Investig Dermatol Symp Proc 8:65–68CrossRefPubMed
48.
Vexiau P, Chaspoux C, Boudou P, Fiet J, Abramovici Y, Rueda MJ, Hardy N, Reygagne P (2000) Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. Arch Dermatol Res 292:598–604CrossRefPubMed
49.
50.
Winiarska A, Mandt N, Kamp H, Hossini A, Seltmann H, Zouboulis CC, Blume-Peytavi U (2006) Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells. Skin Pharmacol Physiol 19:311–321CrossRefPubMed
51.
Yamana K, Labrie F, Luu-The V (2010) Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride. Horm Mol Biol Clin Investig 2:293–299PubMed
52.
53.
Zhou CK, Levine PH, Cleary SD, Hoffman HJ, Graubard BI, Cook MB (2016) Male pattern baldness in relation to prostate cancer-specific mortality: a prospective analysis in the NHANES I epidemiologic follow-up study. Am J Epidemiol 183:210–217CrossRefPubMedPubMedCentral
Metadata
Title
5α-Reductase isozymes and aromatase mRNA levels in plucked hair from young women with female pattern hair loss
Authors
P. Sánchez
C. Serrano-Falcón
J. M. Torres
S. Serrano
E. Ortega
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 1/2018
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-017-1798-0

Other articles of this Issue 1/2018

Archives of Dermatological Research 1/2018 Go to the issue

Original Paper

Is the DLQI appropriate for medical decision-making in psoriasis patients?

Review

Dermal–epidermal separation methods: research implications

Concise Communication

Immunohistochemical distribution of Ki67 in epidermis of thick glabrous skin of human digits

Original Paper

Quality assessment of atopic dermatitis clinical practice guidelines in ≤ 18 years

Original Paper

Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case–control study

Original Paper

Mediterranean diet: fresh herbs and fresh vegetables decrease the risk of Androgenetic Alopecia in males