Topically applied thyroid hormones stimulate hair growth in organ-cultured human scalp skin

We have previously shown that the thyroid hormones triiodothyronine (T3) and thyroxine (T4) prolong anagen, mitigate stem cell apoptosis, and stimulate mitochondrial functions in microdissected human scalp HFs ex vivo. To circumvent the systemic adverse effects of T3/T4, we have asked in the current pilot study whether topically applied T3/T4 retains hair growth-promoting properties. To prove this, we have topically treated healthy full-thickness human scalp skin with T3 (1, 10nM) and T4 (1, 10M) for six days in serum-free organ culture, using an HF-targeting vehicle that contains only FDA-approved ingredients. This showed that, at distinct doses, topical T3 and T4 significantly increased the percentage of HFs in anagen, decreased the percentage of proliferative (Ki-67+) cells in the hair matrix, did not promote melanogenesis (as measured by quantitative Warthin-Starry histochemistry), and significantly increased keratin 15 expression in the bulge. Finally, T3 and T4, at low concentrations, increase the expression of the hair growth promoters IGF-1 and FGF-7. The lower concentration of T3 and both of T4 also significantly increases the number of CD31+ endothelial cells, suggesting a pro-angiogenic effect, which is also important for hair growth promotion. These preliminary results strongly suggest that topically applied thyroid hormones promote hair growth in intact human scalp on multiple levels ex vivo. This invites the intermittent pulse application of topical T3 and T4 as a novel therapeutic intervention for managing hair loss disorders associated with telogen effluvium, such as androgenetic alopecia.