Premium
Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
Author(s) -
Miranda Benjamin H.,
Charlesworth Matthew R.,
Tobin Desmond J.,
Sharpe David T.,
Randall Valerie A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700260rr
Subject(s) - androgen , biology , androgen receptor , organ culture , hair follicle , medicine , endocrinology , hormone , dihydrotestosterone , testosterone (patch) , epigenetics , sexual differentiation , gene , genetics , cancer , prostate cancer , in vitro
Male sex hormones—androgens—regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs ( e.g. , beard). Follicle response is epigenetically varied: some remain unaffected ( e.g. , eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone‐driven cancer, hirsutism, and alopecia. Unfortunately, existing development models are not androgen sensitive. Here, we use hair follicles to establish an androgen‐responsive human organ culture model. We show that women's intermediate facial follicles respond to men's higher androgen levels by synthesizing more hair over several days, unlike donor‐matched, androgen‐insensitive, terminal follicles. We demonstrate that androgen receptors—androgen‐activated gene transcription regulators—are required and are present in vivo within these follicles. This is the first human organ that involves multiple cell types that responds appropriately to hormones in prolonged culture, in a way which mirrors its natural behavior. Thus, intermediate hair follicles offer a hormone‐switchable human model with exceptional, unique availability of genetically identical, but epigenetically hormone‐insensitive, terminal follicles. This should enable advances in understanding sex steroid hormone signaling, gene regulation, and developmental and regenerative systems and facilitate better therapies for hormone‐dependent disorders.—Miranda, B. H., Charlesworth, M. R., Tobin, D.J., Sharpe, D.T., Randall, V. A. Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life. FASEB J. 32, 795–806 (2018). www.fasebj.org