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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

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). Fo...

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Autores principales: Miranda, Benjamin H., Charlesworth, Matthew R., Tobin, Desmond J., Sharpe, David T., Randall, Valerie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Federation of American Societies for Experimental Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928870/
https://www.ncbi.nlm.nih.gov/pubmed/29046359
http://dx.doi.org/10.1096/fj.201700260RR
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author Miranda, Benjamin H.
Charlesworth, Matthew R.
Tobin, Desmond J.
Sharpe, David T.
Randall, Valerie A.
author_facet Miranda, Benjamin H.
Charlesworth, Matthew R.
Tobin, Desmond J.
Sharpe, David T.
Randall, Valerie A.
author_sort Miranda, Benjamin H.
collection PubMed
description 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.
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spelling pubmed-59288702018-05-04 Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life Miranda, Benjamin H. Charlesworth, Matthew R. Tobin, Desmond J. Sharpe, David T. Randall, Valerie A. FASEB J Research 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. Federation of American Societies for Experimental Biology 2018-02 2017-10-18 /pmc/articles/PMC5928870/ /pubmed/29046359 http://dx.doi.org/10.1096/fj.201700260RR Text en © The Author(s) http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Miranda, Benjamin H.
Charlesworth, Matthew R.
Tobin, Desmond J.
Sharpe, David T.
Randall, Valerie A.
Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title_full Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title_fullStr Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title_full_unstemmed Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title_short Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
title_sort androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928870/
https://www.ncbi.nlm.nih.gov/pubmed/29046359
http://dx.doi.org/10.1096/fj.201700260RR
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