Endocrinology, Vol 117, 2106-2113, Copyright © 1985 by Endocrine Society

ARTICLES

Skin is an active site for the inner ring monodeiodination of thyroxine to 3,3',5'-triiodothyronine

TS Huang, IJ Chopra, A Beredo, DH Solomon and TecoGN Chua

T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5-diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5- diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				M. H. A. Kester, G. G. J. M. Kuiper, R. Versteeg, and T. J. Visser Regulation of Type III Iodothyronine Deiodinase Expression in Human Cell Lines Endocrinology, December 1, 2006; 147(12): 5845 - 5854. [Abstract] [Full Text] [PDF]

				A. Hernandez and D. L. St. Germain Dexamethasone Inhibits Growth Factor-Induced Type 3 Deiodinase Activity and mRNA Expression in a Cultured Cell Line Derived from Rat Neonatal Brown Fat Vascular-Stromal Cells Endocrinology, July 1, 2002; 143(7): 2652 - 2658. [Abstract] [Full Text] [PDF]

				A. C. Bianco, D. Salvatore, B. Gereben, M. J. Berry, and P. R. Larsen Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases Endocr. Rev., February 1, 2002; 23(1): 38 - 89. [Abstract] [Full Text] [PDF]

				M. Braga and D. S. Cooper Oral Cholecystographic Agents and the Thyroid J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1853 - 1860. [Abstract] [Full Text]

				A. Slominski and J. Wortsman Neuroendocrinology of the Skin Endocr. Rev., October 1, 2000; 21(5): 457 - 487. [Abstract] [Full Text]

				J. M. Bates, D. L. St. Germain, and V. A. Galton Expression Profiles of the Three Iodothyronine Deiodinases, D1, D2, and D3, in the Developing Rat Endocrinology, February 1, 1999; 140(2): 844 - 851. [Abstract] [Full Text]

				A. Hernandez, D. L. St. Germain, and M. J. Obregon Transcriptional Activation of Type III Inner Ring Deiodinase by Growth Factors in Cultured Rat Brown Adipocytes Endocrinology, February 1, 1998; 139(2): 634 - 639. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, M. J. Obregon, A. Hernandez, F. Escobar del Rey, and G. Morreale de Escobar Regulation of Iodothyronine Deiodinase Activity as Studied in Thyroidectomized Rats Infused with Thyroxine or Triiodothyronine Endocrinology, June 1, 1997; 138(6): 2559 - 2568. [Abstract] [Full Text] [PDF]

				W. Croteau, S. L. Whittemore, M. J. Schneider, and D. L. St. Germain Cloning and Expression of a cDNA for a Mammalian Type III Iodothyronine Deiodinase J. Biol. Chem., July 14, 1995; 270(28): 16569 - 16575. [Abstract] [Full Text] [PDF]