Journal ArticleDOI
The Effects of Propylthiouracil, Iodothyronines, and Other Agents on Thyroid Hormone Metabolism in Human Placenta
Madeleine Fay,Elio Roti,Shih Lieh Fang,George E. Wright,Lewis E. Braverman,Charles H. Emerson +5 more
TLDR
These studies may be relevant to the practice of administering propylthiouracil, propranolol, and iopanoic acid to pregnant women and the effects of drugs and other compounds on human and rat PT4ase.Abstract:
Human and rat placental homogenates contain inner ring deiodinase activity (PT4ase) towards T4 and T3. This activity may decrease the transfer of T4 and T3 across the placenta and influence thyroid hormone disposal in the fetal circulation. Data are now presented on human PT4ase in subcellular fractions, the Km of human PT4ase, and the effects of drugs and other compounds on human and rat PT4ase. The specific activity (nanograms of rT3 produced per min/ mg protein) of each fraction of human placenta was as follows: nuclear, 0.07; mitochondrial, 0.15; lysosomal, 0.19; microsomal, 1.30; and cytosol, 0.01. The apparent Michaelis-Menton (Km) for PT4ase in human placental microsomes was 1.2 × 10-7 M. T3, 3,3′-diiodothyronine, iopanoic acid, iodoacetic acid, diamide, and propranolol all exhibited dose-dependent inhibition of human and rat PT4ase when tested in the presence of 10 mM dithiothreitol (DTT). Propylthiouracil did not inhibit PT4ase at 10 mM DTT, but when the DTT concentration was lowered to 0.25 mM, ...read more
Citations
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Journal ArticleDOI
Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.
TL;DR: The goal of this review is to place the exciting advances that have occurred in understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context.
Journal ArticleDOI
Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes.
TL;DR: An impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea.
Journal ArticleDOI
Placental metabolism and its regulation in health and diabetes
Gernot Desoye,Eleazar Shafrir +1 more
Journal ArticleDOI
Maternal to Fetal Thyroxine Transmission in the Human Term Placenta Is Limited by Inner Ring Deiodination
TL;DR: The hypothesis that placental inner ring (type III) deiodination is a major factor controlling placental transmission of maternal T4 is supported.
Journal ArticleDOI
Topological Analysis of the Integral Membrane Protein, Type 1 Iodothyronine Deiodinase (D1)
TL;DR: It is concluded that the amino terminus of D1 contains uncleaved signal and stop transfer sequence properties and positively charged residues at positions 11, 12, and 27 are required for optimal formation of the protein but not for catalysis.
References
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Journal ArticleDOI
Kinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex
TL;DR: Evidence was obtained for the existence of two thiol-dependent 5'-deiodinase entities that predominates in tissue from euthyroid and long-term hypothyroid rats, and one of these follows "ping-pong" kinetics with dithiothreitol as the cosubstrate, and is inhibited by propylthiouracil (PrSUra) and iodoacetate.
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Subcellular localization of a rat liver enzyme converting thyroxine into tri-iodothyronine and possible involvement of essential thiol groups.
TL;DR: It was shown that thiol groups play an essential role in the conversion of thyroxine into tri-iodothyronine and that the former is indeed of microsomal origin.
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The placental transfer of propylthiouracil, methimazole and carbimazole.
TL;DR: Results from human studies after a single oral dose indicate that, as in the rat, the placenta appeared to be more permeable to 35S-MMI than to35S-PTU as shown by the marked difference in fetal serum:maternal serum ratios and amounts accumulated in the fetus.
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Thyroxine 5′-Deiodinase Activity of Rat Kidney: Observations on Activation by Thiols and Inhibition by Propylthiouracil
TL;DR: Observations suggest that PTU inhibition of T4 5'-deiodinase results from an interaction of PTU with the enzym, possibly via a PTU-enzyme disulfide which can be prevented or reversed by thiols or thioureylene agents, and raise the possibility that protein sulfhydryl groups may undergo oxidation during the reductive 5'- deiodination of L-T4.
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Human Placenta Is an Active Site of Thyroxine and 3,3',5-Triiodothyronine Tyrosyl Ring Deiodination*
TL;DR: Human placental homogenate deiodinates the tyrosyl ring of T4 and T3, converting these active thyroid hormones to the inactive iodothyronines, rT3 from T4, and 3,3'-diiodothyronine and 3'-monoiodothyronsine from T3.