Molecular cloning and characterization of common marmoset SULT1C subfamily members that catalyze the sulfation of thyroid hormones

Author(s):  
Katsuhisa Kurogi ◽  
Yoko Manabe ◽  
Ming-Cheh Liu ◽  
Masahito Suiko ◽  
Yoichi Sakakibara

Abstract Cytosolic sulfotransferase SULT1C subfamily is one of the most flexible gene subfamily during mammalian evolution. The physiological functions of SULT1C enzymes still remain to be fully understood. In this study, common marmoset (Callithrix jacchus), a promising primate animal model, was used to investigate the functional relevance of the SULT1C subfamily. Gene database search revealed three intact SULT1C genes and a pseudogene in its genome. These four genes were named SULT1C1, SULT1C2, SULT1C3P, and SULT1C5, according to the sequence homology and gene location. Since SULT1C5 is the orthologous gene for human SULT1C2P, we propose, here, to revisit the designation of human SULT1C2P to SULT1C5P. Purified recombinant SULT1C enzymes showed sulfating activities toward a variety of xenobiotic compounds and thyroid hormones. Kinetic analysis revealed high catalytic activities of SULT1C1 and SULT1C5 for 3,3’-T2. It appears therefore that SULT1C isoforms may play a role in the thyroid hormone metabolism in common marmoset.

1985 ◽  
Vol 249 (5) ◽  
pp. E519-E524 ◽  
Author(s):  
Z. Glick ◽  
S. Y. Wu ◽  
J. Lupien ◽  
R. Reggio ◽  
G. A. Bray ◽  
...  

The relationship between the meal-induced increase in brown adipose tissue (BAT) thermogenesis, determined by the level of GDP binding to BAT mitochondria, and thyroid hormone metabolism have been examined. A single low-protein, high-carbohydrate meal resulted in a significant increase in the thermogenic activity of BAT. This effect on BAT thermogenesis was accompanied by significant increases in activity of thyroxine 5'-monodeiodinase in the BAT (P less than 0.05) and liver (P less than 0.02) but not with any significant changes in serum concentrations of the thyroid hormones. The stimulatory effects of the meal on BAT thermogenesis and hepatic thyroxine (T4) to triiodothyronine (T3) conversion persisted at least as late as 24 h after meal onset. Food deprivation for 40 h was associated with large reductions in serum concentrations of T3 (P less than 0.01) and T4 (P less than 0.001), but deprivation for 18 h had no significant effect on serum T3 and T4 concentrations. Our data indicate that the meal-induced increase in BAT thermogenesis can be independent from changes in serum concentrations of thyroid hormones and suggest that T3 produced in BAT in response to feeding may play a role in the thermic response of this tissue to meals.


2002 ◽  
Vol 174 (1) ◽  
pp. 111-119 ◽  
Author(s):  
SM van der Heide ◽  
TJ Visser ◽  
ME Everts ◽  
PH Klaren

We have investigated the potential role of fibroblasts in local thyroid hormone metabolism in neonatal rat heart. Incubation of cardiac fibroblasts with thyroxine (T4) or 3,5,3'-tri-iodothyronine (T3) resulted in the appearance of water-soluble metabolites, whereas incubation of cardiomyocytes under the same conditions did not or did so to a much lesser extent. Time-course studies showed that production is already evident after 1-5 h of exposure and that the process equilibrates after 24-48 h. Analysis of the products revealed both the T4 and the T3 metabolites to be glucuronides. These results were corroborated by the detection of uridine diphosphate (UDP)-glucuronyltransferase activity in cardiac fibroblasts. We found no indication for outer ring deiodination in fibroblasts, cardiomyocytes or heart homogenates. From these results we have concluded that cardiac fibroblasts, but not cardiomyocytes, are able to glucuronidate T4 and T3 and secrete the conjugates. This could play a role in local metabolism, e.g. to protect the heart tissue from high levels of thyroid hormones.


2001 ◽  
Vol 22 (4) ◽  
pp. 451-476 ◽  
Author(s):  
Georg Hennemann ◽  
Roelof Docter ◽  
Edith C. H. Friesema ◽  
Marion de Jong ◽  
Eric P. Krenning ◽  
...  

2005 ◽  
Vol 187 (2) ◽  
pp. 257-266 ◽  
Author(s):  
J C Sousa ◽  
G Morreale de Escobar ◽  
P Oliveira ◽  
M J Saraiva ◽  
J A Palha

Thyroid hormones circulate in blood mainly bound to plasma proteins. Transthyretin is the major thyroxine plasma carrier in mice. Studies in transthyretin-null mice revealed that the absence of transthyretin results in euthyroid hypothyroxinemia and normal thyroid hormone tissue distribution, with the exception of the choroid plexus in the brain. Therefore, transthyretin does not influence normal thyroid hormone homeostasis under standard laboratory conditions. To investigate if transthyretin has a buffer/storage role we challenged transthyretin-null and wild-type mice with conditions of increased hormone demand: (i) exposure to cold, which elicits thermogenesis, a process that requires thyroid hormones; and (ii) thyroidectomy, which abolishes thyroid hormone synthesis and secretion and induces severe hypothyroidism. Transthyretin-null mice responded as the wild-type both to changes induced by stressful events, namely in body weight, food intake and thyroid hormone tissue content, and in the mRNA levels of genes whose expression is altered in such conditions. These results clearly exclude a role for transthyretin in thyroid hormone homeostasis even under conditions of increased hormone demand.


1987 ◽  
Vol 112 (1) ◽  
pp. 171-175 ◽  
Author(s):  
C. Liniger ◽  
D. Pometta ◽  
A. G. Burger

ABSTRACT SR-202 is a non-iodinated potential lipid-altering agent. When administered (100 mg) three times per day for 3 days to six euthyroid subjects it was associated with a 30 ± 3% (mean ± s.e.m.) fall in 3,3′,5-tri-iodothyronine(T3)(P < 0·001), a reciprocal 104 ± 14% rise in 3,3′,5′-tri-iodothyronine (reverse T3, rT3) (P < 0·01), and a 37 ± 7% rise in thyroxine (T4) (P < 0·001). Basal and TRH-stimulated TSH did not change. These results suggested that SR-202 was acting as an inhibitor of the peripheral monodeiodination of T4 to T3. During a second study the same subjects received the same dose of SR-202 for a further 3 days following 15 days of progressive substitutive treatment with l-T4, which they continued to take at 200 μg/day until the end of the study. Despite higher levels of thyroid hormones in the substituted subjects, similar results were observed, serum T3 falling by 40 ± 2% (P < 0·001), serum rT3 and T4 rising by 168 ± 24% (P < 0·01) and 37 ± 9% (P < 0·01) respectively. These changes provide compelling evidence that SR-202 is an inhibitor of the peripheral conversion of T4 to T3 that acts on thyroid hormone metabolism without provoking a counter-regulatory pituitary response. It might prove to be a useful tool for the clinical investigation of thyroid function. J. Endocr. (1987) 112, 171–175


2006 ◽  
Vol 26 (6) ◽  
pp. 2317-2326 ◽  
Author(s):  
Ivan del Barco Barrantes ◽  
Ana Montero-Pedrazuela ◽  
Ana Guadaño-Ferraz ◽  
Maria-Jesus Obregon ◽  
Raquel Martinez de Mena ◽  
...  

ABSTRACT dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity.


1976 ◽  
Vol 56 (2) ◽  
pp. 233-242 ◽  
Author(s):  
L. J. FISHER ◽  
DOROTHY S. WALSH

Sixteen lactating Holstein cows were randomly assigned to treatment sequences in a 4 × 4 changeover experiment. Experimental periods were 28 days in length separated by 7 days for changeover. Cows were fed corn silage free choice and gradually increasing amounts of one of four dairy concentrates containing 0, 11, 22, or 34% rapeseed meal (RSM) of a Canadian, experimental, low glucosinolate–low erucic acid variety. Concentrate intake (kg dry matter/day), milk yield (kg/day) and body weight change (kg/28 days) were 8.45a, 8.71a, 8.37a and 7.17b; 24.40a, 24.03ab, 22.92bc and 21.96c and 7.6b, 22.4b, 13.0ab, and 3.0b for 0, 11, 22 and 34% RSM mixtures, respectively. There was no influence of treatment on milk composition. Ration dry matter (DM) and nitrogen digestibilities declined (P < 0.05) as the RSM in the concentrate mixture increased. The amount of nitrogen excreted in the urine was greatest for cows fed 0% RSM and least for cows fed 34% RSM. Cows fed concentrate mixtures containing 34% RSM had a lower blood thyroxine level than others (P < 0.05), but RSM-containing concentrates had no apparent effect on the conversion of thyroxine to triiodothyronine. Results of the trial indicated that this experimental variety of RSM had no detrimental effect on concentrate intake, DM digestibility, milk composition or thyroid hormone metabolism when included at levels up to 22% in the concentrate mixture. However, milk yield and apparent digestibility of ration nitrogen were decreased (P < 0.05) by the 22% RSM mixture. It was not certain from the current findings whether the depression in digestibility was due largely to the high oil content of the meal or due to the higher fiber content of the RSM-supplemented rations.


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