Biochemical Mechanisms of Thyroid Hormone Deiodination

Kuiper, George G. J. M.; Kester, Maartje I.; Peeters, Robin P.; Visser, Theo J.

doi:10.1089/thy.2005.15.787

Cited by 155 publications

(117 citation statements)

References 97 publications

(127 reference statements)

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“…Although many details remain to be confirmed, a conservative interpretation of these results is that the thyronamines T1AM and T0AM are naturally occurring relatives of TH that might be generated by the concerted actions of aromatic acid decarboxylase and the three TH deiodinases that have been described (Visser et al, 1994;Kuiper et al, 2000;Kalsbeek et al, 2005;Köhrle, 2005;Moreno, et al, 2005). However, the possibility that alternative routes of thyronamine biosynthesis exist must also be explored.…”

Section: Thermoregulation and Metabolism-mentioning

confidence: 99%

Trace amine-associated receptor 1—Family archetype or iconoclast?

Grandy

2007

Pharmacology & Therapeutics

179

211

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Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the 'trace amines' (TAs) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of two publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers as TA1 (Borowsky et al., 2001) and TAR1 (Bunzow et al., 2001). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines recombinant rodent and human TA receptors dosedependently couple to the stimulation of cAMP production. Structure-activity profiling based on this functional response has revealed that in addition to the TAs, other biologically active compounds containing a 2 carbon aliphatic side chain linking an amino group to at least one benzene ring are potent and efficacious TA receptor agonists with amphetamine, methamphetamine, 3-iodothyronamine, thyronamine, and dopamine among the most notable. Almost 100 years after the search for TA receptors began numerous TA1/TAR1-related sequences, now called Trace AmineAssociated Receptors (TAARs), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TA receptor a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCRs. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

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Section: Thermoregulation and Metabolism-mentioning

confidence: 99%

Trace amine-associated receptor 1—Family archetype or iconoclast?

Grandy

2007

Pharmacology & Therapeutics

179

211

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“…Iodothyronine Deiodinases-Three DIOs have been identified with a tissue and subcellular localization (34). DIO1 is found primarily in the liver, kidney, and thyroid; DIO2 is in the brain, pituitary, thyroid, skeletal muscle, and brown adipose tissue; and DIO3 is found in the cerebral cortex and skin and is expressed at a very high level in the placenta and pregnant uterus.…”

Section: Structure and Activity Of Mammalian Selenoproteinsmentioning

confidence: 99%

“…DIO1 and DIO2 catalyze the deiodination of T 4 , the major thyroid hormone secreted by the thyroid gland, into the active hormone T 3 ; DIO3 converts T 4 into reverse T 3 and also T 3 into 3,3Ј-diidothyronine. DIO1 and DIO2 can also convert reverse T 3 into 3,3Ј-diidothyronine (34,35).…”

Section: Structure and Activity Of Mammalian Selenoproteinsmentioning

confidence: 99%

Selenoproteins

Holmgren

2009

Journal of Biological Chemistry

596

366

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Selenium is an essential micronutrient for man and animals. The role of selenium has been attributed largely to its presence in selenoproteins as the 21st amino acid, selenocysteine (Sec, U). Sec is encoded by TGA in DNA. A unique mechanism is used to decode the UGA codon in mRNA to co-translationally incorporate Sec into the growing polypeptide because there is no free pool of Sec. In the human genome, 25 genes for selenoproteins have been identified. Selenoproteins such as glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases are involved in redox reactions, and Sec is an active-site residue essential for catalytic activity. Selenoproteins have biological functions in oxidoreductions, redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses.

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“…Most of the hormone released is in the form of T4, as total serum T4 is 40-fold higher than serum T3. The main pathway for the production of the bioactive form, T3, is via outer ring deiodination of the prohormone T4 by iodothyronine deiodinases (15). This activation reaction is catalyzed by types 1 and 2 deiodinases (D1 and D2) in peripheral tissues.…”

Section: Thyroid Hormonesmentioning

confidence: 99%

Clinical implications of altered thyroid status in male testicular function

Wajner

Wagner

Maia

2009

Arq Bras Endocrinol Metab

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Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function. RESUMOOs hormônios da tireoide estão envolvidos virtualmente no desenvolvimento e na manutenção de todos os tecidos. As gônadas masculinas foram, por décadas, consideradas insensíveis aos hormônios tireoidianos. No entanto, estudos mais recentes têm demonstrado que disfunções tireoidianas estão associadas não somente a anormalidades na morfologia e na função dos testículos, mas também à diminuição da fertilidade e alterações na atividade sexual masculina. Atualmente, o papel da triiodotironina (T3) no controle da proliferação das células de Sertoli e Leydig, maturação testicular e esteroidogênese é amplamente aceito, bem como a presença de transportadores e receptores para o hormônio tireoidiano nos testículos durante o período de desenvolvimento e a idade adulta. No entanto, apesar dos dados que indicam que o T3 atua diretamente nos testículos humanos, persistem controvérsias em relação ao impacto das doenças tireoidianas sobre a espermatogênese e a fertilidade, o que pode ser em parte devido à escassez de estudos clínicos nessa área. Essa revisão tem por objetivo apresentar um panorama de dados clínicos atualizados sobre o papel dos hormônios tireoidianos na função gonadal masculina. Arq Bras Endocrinol Metab. 2009;53(8):976-82 Descritores

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Biochemical Mechanisms of Thyroid Hormone Deiodination

Cited by 155 publications

References 97 publications

Trace amine-associated receptor 1—Family archetype or iconoclast?

Trace amine-associated receptor 1—Family archetype or iconoclast?

Selenoproteins

Clinical implications of altered thyroid status in male testicular function

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