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    Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life

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    Publication date
    2018-02-05
    Author
    Miranda, Benjamin H.
    Charlesworth, Matthew R.
    Tobin, Desmond J.
    Sharpe, David T.
    Randall, Valerie A.
    Keyword
    Alopecia; Balding; Hirsutism; Intermediate hair follicles; Model system
    Rights
    (c) 2018 The Authors. This is an Open Access article distributed under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by-nc/4.0/)
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    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.
    URI
    http://hdl.handle.net/10454/14146
    Version
    Published version
    Citation
    Miranda BH, Charlesworth MR, Tobin DJ et al (2018) Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life. FASEB Journal. 32: 795-806.
    Link to publisher’s version
    https://doi.org/10.1096/fj.201700260RR
    Type
    Article
    Collections
    Life Sciences Publications

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