title: Role for inner ring deiodination preventing transcutaneous passage of thyroxine.
abstract: Creams containing thyroid hormone are commonly employed for cosmetic purposes. To verify whether T(4) applied to the skin surface can enter the bloodstream either directly or as a metabolite, a cream containing L-T(4) [3,5,3',5'-tetraiodothyronine (T(4))] was self-applied by volunteers for 2 wk. No significant variations in urinary iodide, TSH, and serum (total and free) T(4) and T(3) concentrations were observed at any time relative to pretreatment values, whereas rT(3) concentrations increased significantly 6 and 12 h after cream application. The increased rT(3) 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 T(4) 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 T(4), and T(3) was not detected. We then measured D3 activity in a surgical skin specimen. The K(m) for T(3) was 1.74 nmol/liter, and the maximum velocity was 23.5 fmol/microg microsomal protein/h. In conclusion, our study indicates that normal human skin serves as a substantial, but incomplete, barrier to T(4) passage. D3 plays an important role in augmenting T(4) blockade by inactivating T(4) to rT(3).
authors.affiliation: Department of Endocrinology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Santini
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ceccarini
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Lucia
authors.initials: L
authors.lastname: Montanelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gatti
authors.forename: Veronica
authors.initials: V
authors.lastname: Rosellini
authors.forename: Claudia
authors.initials: C
authors.lastname: Mammoli
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
authors.forename: Inder J
authors.initials: IJ
authors.lastname: Chopra
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Safer
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Braverman
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
mesh_terms: D000042:Absorption; D000328:Adult; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008081:Liposomes; D009824:Ointments; D012867:Skin / Q000201:enzymology; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D008081:Liposomes; D009824:Ointments; D014284:Triiodothyronine; D007455:Iodine; D007453:Iodide Peroxidase; D013974:Thyroxine