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Role for Inner Ring Deiodination Preventing Transcutaneous Passage of Thyroxine

Departments of Endocrinology (F.S., P.V., G.C., L.M., V.R., C.M., E.M., A.P.), Pharmaceutical Sciences (M.M.), and Plastic Surgery (G.G.), University of Pisa, 56124 Pisa, Italy; Endocrinology Unit, University of Pavia, Fondazione Salvatore Maugeri IRCCS (L.C.), Pavia, Italy; Department of Endocrinology, University of California (I.J.C.), Los Angeles, California 90095; and Section of Endocrinology, Boston University School of Medicine (J.D.S., L.E.B.), Boston, Massachusetts 02118

Address all correspondence and requests for reprints to: Dr. Ferruccio Santini, Department of Endocrinology, University of Pisa, Via Paradisa, 2, 56124 Pisa, Italy.

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 K_m for T₃ was 1.74 nmol/liter, and the maximum velocity was 23.5 fmol/µg microsomal protein/h. In conclusion, our study indicates that normal human skin serves as a substantial, but incomplete, barrier to T₄ passage. D3 plays an important role in augmenting T₄ blockade by inactivating T₄ to rT₃.

Abbreviations: D3, Type III deiodinase; T₂, 3,3'-diiodothyronine.

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