Thyroid hormone action on skin

Safer, Joshua D.

doi:10.1097/med.0b013e328357b45e

Cited by 34 publications

(34 citation statements)

References 97 publications

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“…Topical application of T 4 is expected to reduce the well-known adverse effects associated with elevated systemic TH levels (Kharlip and Cooper, 2009;Taylor et al, 2013;Walrand et al, 2014). Interestingly, topical T 3 has already been shown to promote murine skin wound healing and hair growth in vivo (Safer, 2012;Safer et al, 2005), while a topically applied TH analogue counteracted glucocorticoid-induced human skin atrophy (Yazdanparast et al, 2006).…”

Section: Discussionmentioning

confidence: 98%

“…However, it is unlikely that the putative anti-aging effects of THs can be explained by wound healing inhibition. THs actually promote wound healing, a highly energy-consumptive process, in murine skin in vivo (Kassem et al, 2012;Safer, 2012;Safer et al, 2005) and promotes reepithelialization in experimentally wounded organ-cultured human skin (Meier et al, 2013) ex vivo (Paus lab, unpublished observation), while mice devoid of the TR-alpha and -beta show retarded wound-healing (Contreras-Jurado et al, 2014;Safer et al, 2005). Moreover, all in situ analyses reported here where purposely performed distant from the periphery of the organ-cultured skin fragments, thus lowering the risk to confound aging-related phenomena with superimposed wound M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 9 healing processes (for detailed discussion of wound healing-related skin responses as a potential confounding element in the current study, see Supplementary Text S1).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…They operate as key regulators of human energy metabolism and stimulate mitochondrial activity and biogenesis in many different organs (Cioffi et al, 2013;Johannsen et al, 2012;Norman and Henry, 2015;Weitzel et al, 2003;Yehuda-Shnaidman et al, 2014). Yet, although mammalian skin is a prominent target organ of thyroid hormones (THs) in health and disease (Antonini et al, 2013;Contreras-Jurado et al, 2011;Ramot et al, 2009;Safer, 2012;van Beek et al, 2008), it remains unknown whether and how THs impact on mitochondrial function in human epidermis.…”

Section: Introductionmentioning

confidence: 99%

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Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Vidali

Chéret

Giesen

et al. 2016

Journal of Investigative Dermatology

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Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L). Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria. Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity. Increased mitochondrial function can correlate with increased reactive oxygen species production, DNA damage, and accelerated tissue aging. However, THs neither raised reactive oxygen species production or matrix metalloproteinase-1, -2 and -9 activity nor decreased sirtuin1 (Sirt1) immunoreactivity. Instead, triiodothyronine increased sirtuin-1, fibrillin-1, proliferator-activated receptor-gamma 1-alpha (PGC1α), collagen I and III transcription, and thyroxine decreased cyclin-dependent kinase inhibitor 2A (p16(ink4)) expression in organ-cultured human skin. Moreover, TH treatment increased intracutaneous fibrillin-rich microfibril and collagen III deposition and decreased mammalian target of rapamycin (mTORC1/2) expression ex vivo. This identifies THs as potent endocrine stimulators of mitochondrial function in human epidermis, which down-regulates rather than enhance the expression of skin aging-related biomarkers ex vivo. Therefore, topically applied THs deserve further exploration as candidate agents for treating skin conditions characterized by reduced mitochondrial function.

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Section: Discussionmentioning

confidence: 98%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Vidali

Chéret

Giesen

et al. 2016

Journal of Investigative Dermatology

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“…In hyperthyroid individuals, skin often presents with some of the following symptoms: softness, perspiration, heat, itching, generalized pruritus, chronic urticaria, vitiligo, and diffuse skin pigmentation (109, 110). In addition, the epidermis is usually thinner than normal.…”

Section: Regulation Of Gene Expression By Thyroid Hormone In the Skinmentioning

confidence: 99%

“…In hypothyroid subjects, the skin is dry, cold, and rough. The epidermis is hyperkeratotic, alopecia may develop, and there is diffuse myxedema (110). …”

Section: Regulation Of Gene Expression By Thyroid Hormone In the Skinmentioning

confidence: 99%

An Intimate Relationship between Thyroid Hormone and Skin: Regulation of Gene Expression

Antonini¹,

Sibilio²,

Dentice³

et al. 2013

Front. Endocrinol.

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Skin is the largest organ of the human body and plays a key role in protecting the individual from external insults. The barrier function of the skin is performed primarily by the epidermis, a self-renewing stratified squamous epithelium composed of cells that undergo a well-characterized and finely tuned process of terminal differentiation. By binding to their receptors thyroid hormones (TH) regulate epidermal cell proliferation, differentiation, and homeostasis. Thyroid dysfunction has multiple classical manifestations at skin level. Several TH-responsive genes, as well as genes critical for TH metabolism and action, are expressed at epidermal level. The role of TH in skin is still controversial, although it is generally recognized that TH signaling is central for skin physiology and homeostasis. Here we review the data on the epidermis and its function in relation to TH metabolism and regulation of gene expression. An understanding of the cellular and molecular basis of TH action in epidermal cells may lead to the identification of putative therapeutical targets for treatment of skin disorders.

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The Skin and Endocrine Disorders

Paus

2016

Rook's Textbook of Dermatology, Ninth Edition

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Given that the skin is a major target organ of numerous hormones for which it expresses functional receptors, it is not surprising that excessive or insufficient systemic levels of these hormones induce clinically relevant cutaneous responses. These can manifest as general skin symptoms and signs such as pruritus, skin dryness, seborrhoea, hair loss, hypertrichosis, hirsutism, hyperhidrosis and/or hyperpigmentation, any of which prompts consideration of an underlying endocrine disease. In addition, characteristic skin lesions such as palmar erythema, gingival hyperpigmentation, stretch marks (striae distensae), acanthosis nigricans, pretibial myxoedema, necrobiosis lipoidica, melasma and acneform eruptions provide invaluable diagnostic clues to the possibility of unrecognized endocrine disease. More recently, the field has been revolutionized by the recognition that human skin is also a major endocrine and neuroendocrine organ which produces and/or metabolizes not only all classes of steroid hormones but also multiple peptide (neuro‐) hormones, neuropeptides and neurotransmitters. These impact profoundly on skin physiology and pathology at multiple levels, ranging from skin barrier function and neurogenic skin inflammation via wound healing to cutaneous stress responses. This has important implications for future dermatological therapy.

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Thyroid hormone action on skin

Cited by 34 publications

References 97 publications

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

An Intimate Relationship between Thyroid Hormone and Skin: Regulation of Gene Expression

The Skin and Endocrine Disorders

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