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The Hair Follicle as an Estrogen Target and Source

Department of Dermatology (U.O.), University Hospital Hamburg-Eppendorf, University of Hamburg, D-20246 Hamburg, Germany; Department of Paediatric Haematology and Oncology (M.U.), Hannover Medical School, D-30625 Hannover, Germany; Department of Biosciences and Nutrition (J.I., J.-Å.G.), Karolinska Institute, Novum, SE-14186 Stockholm, Sweden; and Department of Dermatology (R.P.), University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, D-23538 Lübeck, Germany

Correspondence: Address all correspondence and reprint requests to: Ralf Paus, M.D., Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. E-mail: ralf.paus{at}derma.uni-luebeck.de

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, it has long been known that 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, 17ß-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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