Role for inner ring deiodination preventing transcutaneous passage of thyroxine.
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).
Santini
Ferruccio
F
Department of Endocrinology, University of Pisa, 56124 Pisa, Italy.
Vitti
Paolo
P
Chiovato
Luca
L
Ceccarini
Giovanni
G
Macchia
Marco
M
Montanelli
Lucia
L
Gatti
Gianluca
G
Rosellini
Veronica
V
Mammoli
Claudia
C
Martino
Enio
E
Chopra
Inder J
IJ
Safer
Joshua D
JD
Braverman
Lewis E
LE
Pinchera
Aldo
A
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
D007527:Isoenzymes; D008081:Liposomes; D009824:Ointments; D014284:Triiodothyronine; D007455:Iodine; D007453:Iodide Peroxidase; D013974:Thyroxine