Role for Inner Ring Deiodination Preventing Transcutaneous Passage of Thyroxine

Creams containing thyroid hormone are commonly employed for cosmetic purposes. To verify whether T4 applied to the skin surface can enter the bloodstream either directly or as a metabolite, a cream containing l-T4 [3,5,3′,5′-tetraiodothyronine (T4)] was self-applied by volunteers for 2 wk. No significant variations in urinary iodide, TSH, and serum (total and free) T4 and T3 concentrations were observed at any time relative to pretreatment values, whereas rT3 concentrations increased significantly 6 and 12 h after cream application. The increased rT3 concentration led us to investigate the presence of inner ring type III deiodinase (D3) activity in human skin. Using human surgical discard skin, we found that T4 can be carried across human epidermis in a liposome cream. Substantial inner ring deiodination was suggested by the fact that only 10% of transferred thyroid hormone remained as T4, and T3 was not detected. We then measured D3 activity in a surgical skin specimen. The Km for T3 was 1.74 nmol/liter,...