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 (T₃) treated mice. To distinguish skin effects of directly applied T₃ from those of systemic hyperthyroidism, we treated CD-1 mice with either intraperitoneally (IP) or topically administered T₃. Relative to controls, mice receiving T₃ IP had 10% thinner epidermis(p < 0.01) and 48% fewer hairs (p < 0.001). By contrast, mice receiving T₃ 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 T₃ effect on proliferation of isolated keratinocyte cultures versus keratinocytes cocultured with dermal fibroblasts. For keratinocytes grown in the absence of fibroblasts, T₃ stimulated proliferation in a dose-dependent, biphasic pattern with the peak at 0.5 nM T₃ (84 ± 30%, p < 0.05). Paradoxically, T₃ inhibited proliferation of keratinocytes cocultured with fibroblasts, the nadir at 0.1 nM T₃ (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 T₃ stimulated keratinocyte proliferation, T₃ 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.