Thyroid Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte Proliferation and Hair Pigmentation

Abstract

Context: Both insufficient and excess levels of thyroid hormones (T 3 and T 4 ) can result in altered hair/skin structure and function (e.g. effluvium). However, it is still unclear whether T 3 and T 4 exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T 3 /T 4 stimulation.Objective: Our objective was to asses the impact of T 3 /T 4 on human HF in vitro. Methods:Human anagen HFs were isolated from skin obtained from females undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr (average, 56 yr) were cultured and treated with T 3 /T 4 . Results:Studying microdissected, organ-cultured normal human scalp HFs, we show here that T 4 up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T 3 and T 4 . T 4 also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-␤2, the key anagen-inhibitory growth factor. Because we show here that human HFs transcribe deiodinase genes (D2 and D3), they may be capable of converting T 4 to T 3 . Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T 3 and T 4 (CK6 is enhanced, CK14 down-regulated). Both T 3 and T 4 also significantly stimulate intrafollicular melanin synthesis. Conclusions:Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T 3 and/or T 4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation. (J Clin Endocrinol Metab 93: 4381-4388, 2008) C linically, it has long been observed that patients with thyroid dysfunction may show prominent hair abnormalities (1-4) and several in vivo studies have demonstrated (partially conflicting) hair growth-modulatory effects of thyroid hormone (TH) in sheep, rats, and mice (5-8). In humans, hypothyroidism can be associated with telogen effluvium, along with the presentation of dry, brittle, and dull hair shafts (2-4). Confusingly, hyperthyroid states can also lead to effluvium, together with thinned hair shaft diameter and brittle, greasy hair (1, 9 -11), despite an apparently increased hair matrix proliferation (3). Hair shafts of patients with hyperthyroidism also show substantially reduced tensile strength (10). Early graying has been claimed to be related to autoimmune thyroid disease, hypothyroidism, and hyperthyroidism (11, 12), whereas darkening of

Endocrine controls of keratin expression

“…(43,44) In hyperthyroidism, skin changes include erythema, palmoplantar hyperhidrosis, acropathy, and infiltrative dermopathy; also, Graves' disease may be associated with generalized pruritus, chronic urticaria, alopecia areata, vitiligo, and diffuse skin pigmentation. In hypothyroidism, the skin is cool, dry with a pasty appearance.…”

“…Not surprisingly, TH effects were also seen on keratin proteins in the HF, demonstrating regulation of the recognized THresponsive keratins in the ORS of the HF. (44) Table 3 summarizes the recognized regulation of keratin gene expression by TH.…”

“…(54,55) In addition, vitamin D may up-regulate a number of key proteins involved directly in differentiation via its specific nuclear receptor, a transcription factor that belongs to the steroid hormone receptor superfamily and that exerts its effects by binding to specific DNA sequences-the vitamin D response elements (VDRE). Hair abnormalities (44) Through its differentiating properties and effects on keratins, vitamin D may also have anti-cancer properties. The absence of VDR led to induction of undifferentiated basal cell carcinomas, (58) and a keratin gene was found to be upregulated by D3 in a model for human colon cancer cells.…”

Fundamental hair follicle biology and fine fibre production in animals

“…It is incorporated in the active site of enzymes such the deiodinases which convert thyroxine to its active form, triiodothyronine, which is essential for development and activity of hair follicles (Rhind and Kyle, 2004;Tiede et al, 2009). Iodine is also essential for synthesis of such thyroid hormones, which have recently been shown to modulate cycle behaviour and pigment production in cultured human scalp hair follicles (van Beek et al, 2008) Copper also has an important enzymatic role (Danks, 1991), for example, in the production of crosslinks in elastin and collagen fibres in the dermis, melanin pigment production in melanocytes (as a component of tyrosinase), post-translational formation of di-suphide bonds between cysteine molecules in cytoskeletal proteins of cortical and cuticle proteins and a role in the formation of crimp in wool. Zinc has an important function in 'zinc finger' structures, which stabilise proteins or peptides and provide DNA recognition sites in regulatory molecules such as transcription factors.…”

Biology of Human Hair: Know Your Hair to Control It

“…Human hair is deeply affected by the level of unbound thyroid hormones that have been described to prolong the duration of anagen, up-regulate the proliferation of Mx keratinocytes and also stimulate intrafollicular melanin synthesis [101,116,117]. On the other hand, several studies reveal that a significant percentage of patients presenting hair loss were diagnosed as suffering from hypothyroidism [118,119].…”