title: Impaired hair growth and wound healing in mice lacking thyroid hormone receptors.
abstract: Both clinical and experimental observations show that the skin is affected by the thyroidal status. In hypothyroid patients the epidermis is thin and alopecia is common, indicating that thyroidal status might influence not only skin proliferation but also hair growth. We demonstrate here that the thyroid hormone receptors (TRs) mediate these effects of the thyroid hormones on the skin. Mice lacking TRα1 and TRβ (the main thyroid hormone binding isoforms) display impaired hair cycling associated to a decrease in follicular hair cell proliferation. This was also observed in hypothyroid mice, indicating the important role of the hormone-bound receptors in hair growth. In contrast, the individual deletion of either TRα1 or TRβ did not impair hair cycling, revealing an overlapping or compensatory role of the receptors in follicular cell proliferation. In support of the role of the receptors in hair growth, TRα1/TRβ-deficient mice developed alopecia after serial depilation. These mice also presented a wound-healing defect, with retarded re-epithelialization and wound gaping, associated to impaired keratinocyte proliferation. These results reinforce the idea that the thyroid hormone nuclear receptors play an important role on skin homeostasis and suggest that they could be targets for the treatment of cutaneous pathologies.
authors.affiliation: Department of Physiopathology of the Endocrine and Nervous Systems, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Contreras-Jurado
authors.affiliation: Department of Physiopathology of the Endocrine and Nervous Systems, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Serrano
authors.affiliation: Molecular Oncology Unit, Division of Biomedicine, CIEMAT, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Martínez-Fernández
authors.affiliation: Department of Physiopathology of the Endocrine and Nervous Systems, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz-Llorente
authors.affiliation: Molecular Oncology Unit, Division of Biomedicine, CIEMAT, Madrid, Spain.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Paramio
authors.affiliation: Department of Physiopathology of the Endocrine and Nervous Systems, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Aranda
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D017353:Gene Deletion; D015870:Gene Expression; D056726:Genetic Association Studies; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000254:growth & development / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011988:Receptors, Thyroid Hormone / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000172:deficiency / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta