Thyroid Hormone Action on Skin: Diverging Effects of Topical versus Intraperitoneal Administration

Abstract

Previously, we demonstrated stimulation of epidermal proliferation and hair growth in triiodothyronine (T(3)) treated mice. To distinguish skin effects of directly applied T(3) from those of systemic hyperthyroidism, we treated CD-1 mice with either intraperitoneally (IP) or topically administered T(3). Relative to controls, mice receiving T(3) IP had 10% thinner epidermis (p < 0.01) and 48% fewer hairs (p < 0.001). By contrast, mice receiving T(3) topically had 78% thicker epidermis (p < 0.01) and 160% more hairs (p < 0.01). To gain insight into factors responsible for the diverging effects, we contrasted T(3) effect on proliferation of isolated keratinocyte cultures versus keratinocytes cocultured with dermal fibroblasts. For keratinocytes grown in the absence of fibroblasts, T(3) stimulated proliferation in a dose-dependent, biphasic pattern with the peak at 0.5 nM T(3) (84 +/- 30%, p < 0.05). Paradoxically, T(3) inhibited proliferation of keratinocytes cocultured with fibroblasts, the nadir at 0.1 nM T(3) (34% +/- 4%, p < 0.001). These studies are the first describing divergent effects of IP and topically administered thyroid hormone. The data suggest that while T(3) stimulated keratinocyte proliferation, T(3) also stimulated proliferation inhibitory factor(s) from skin fibroblasts. Insight into the interplay among the competing factors will be important in understanding thyroid hormone regulation of skin physiology.

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

“…The function of THs in controlling the balance between cell proliferation and cell differentiation in the skin has proven to be puzzling. In fact, reports have indicated that they are essential for optimal epidermal cell proliferation (Safer et al, 2003;Safer, 2005). In vitro, T3 stimulates keratinocyte proliferation.…”

“…In vitro, T3 stimulates keratinocyte proliferation. In vivo, topical T3 stimulates epidermal proliferation, dermal thickening and hair growth (Safer et al, 2001;Safer et al, 2003;Safer, 2005). Topical triac (tri-iodothyroacetic acid) thickens skin by stimulating the production of collagen (Faergemann et al, 2002;Yazdanparast et al, 2004).…”

Thyroid Autoimmunity in Patients with Skin Disorders

“…Thyroid hormone is an important regulator of epidermal homeostasis. In tissue culture studies using surrogates for DNA expression, T 3 has been shown to stimulate growth of both epidermal keratinocytes and dermal fibroblastes [3,4]. In addition, thyroid hormone appears to be necessary for both the initiation and maintenance of hair growth and normal secretion of sebum.…”

The Effects of Topical Application of Thyroid Hormone (Liothyronine, T3) on Skin Wounds in Diabetic Wistar Rats

“…First, hypothyroidism is associated with retarded wound repair probably through decreasing collagen synthesis and or keratinocyte proliferation [21,23,24] which is reversible with thyroid hormone replacement [21,25]. Second, in vitro and in vivo studies have designated that thyroid hormones stimulate keratinocyte and epidermal proliferation as well as hair growth [20,21,26]. Finally, it has been shown that daily treatment with 150 ng topical T3 in mice improves wound closure significantly [19].…”

“…T4 is converted by intracellular thyroid hormone deiodinases to T3, the active thyroid hormone, T3 [15,16]. Apikoglu-Rabus et al revealed that liothyronine (T3), the active thyroid hormone, accelerate wound healing in mice [17] and it is probably through proliferation of keratinocytes [18][19][20][21]. However, to date, no information about effects of thyroid hormones on diabetic wounds is available.…”