TY - JOUR
T1 - The hair follicle as an estrogen target and source
AU - Ohnemus, Ulrich
AU - Uenalan, Murat
AU - Inzunza, José
AU - Gustafsson, Jan Åke
AU - Paus, Ralf
PY - 2006
Y1 - 2006
N2 - For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, ithaslongbeenknownthat estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17β-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.
AB - For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, ithaslongbeenknownthat estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17β-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.
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U2 - 10.1210/er.2006-0020
DO - 10.1210/er.2006-0020
M3 - Review article
C2 - 16877675
AN - SCOPUS:33750096487
SN - 0163-769X
VL - 27
SP - 677
EP - 706
JO - Endocrine Reviews
JF - Endocrine Reviews
IS - 6
ER -