3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes

Schanze, Nancy; Jacobi, Simon F.; Rijntjes, Eddy; Mergler, Stefan; Olmo, Marta del; Hoefig, Carolin S.; Khajavi, Noushafarin; Lehmphul, Ina; Biebermann, Heike; Mittag, Jens; Köhrle, Josef

doi:10.1089/thy.2016.0182

Cited by 20 publications

(36 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…or vehicle [5, 12]. No effect of 3-T 1 AM treatment was observed on Se concentration in the tissues tested (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Hereby, we provided evidence that the ethylamine side chain is indispensable for the rapid cardiac and thermogenic effects of 3-T 1 AM. In vitro data show that 3-T 1 AM is also a substrate for Dio1 and Dio3 enzymes, resulting in the noniodinated T 0 AM [2, 5]. Therefore, we were interested whether deiodination could also constitute an inactivation mechanism for 3-T 1 AM.…”

Section: Discussionmentioning

confidence: 99%

“…Parts of this experiment have been published before [5, 12]. Tissue samples were collected for trace element analysis 24 h after the last injection.…”

Section: Methodsmentioning

confidence: 99%

“…Primer sequences are published or available on request [5, 9]. For the statistical analysis, significant outliers were determined using a Grubbs test (GraphPad software) and excluded.…”

Section: Methodsmentioning

confidence: 99%

“…The biosynthesis of T 0 AM occurs mainly from 3-T 1 AM via inner ring deiodination by deiodinase 3 (Dio3) [2], but the recently described inhibition of T 0 AM synthesis by 6-propyl-2-thiouracil indicates an additional involvement of Dio1 [5]. T 0 AM neither binds to nor activates nuclear TH receptors [1]; however, T 0 AM may activate the trace amine-associated receptor 1, an amine-activated G protein-coupled receptor located in the cell membrane [1].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice

et al. 2017

Self Cite

View full text Add to dashboard Cite

Objectives: Thyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-T₁AM) and iodine-free thyronamine (T₀AM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-T₁AM, the role of T₀AM has been studied less intensively. Study Design: We determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated administration (5 mg/kg/day, i.p., for 7 days) of T₀AM affects metabolism, cardiovascular function, or thermoregulation in male C57BL/6J mice. Since selenium (Se) is important for proper TH function and Se metabolism is affected by TH, we additionally analyzed Se concentrations in liver, serum, and kidney using total reflection X-ray analysis. Results: A single injection of T₀AM had no effect on heart rate, temperature, or activity as assessed by radio telemetry. Likewise, daily administration of T₀AM did not alter body weight, food or water intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body temperature, and no significant differences in hepatic glycogen content or mRNA expression of genes involved in cardiovascular function or metabolic control were determined. Also, the X-ray analysis of Se concentrations revealed no significant changes. However, hepatic T₀AM was significantly increased in the treated animals. Conclusions: In summary, our data demonstrate that T₀AM elicits no obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As T₀AM does also not interfere with TH or Se metabolism, we conclude that the deiodination of 3-T₁AM to T₀AM constitutes an efficient inactivation mechanism, terminating the actions of the more powerful precursor.

show abstract

“…or vehicle [5, 12]. No effect of 3-T 1 AM treatment was observed on Se concentration in the tissues tested (Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Parts of this experiment have been published before [5, 12]. Tissue samples were collected for trace element analysis 24 h after the last injection.…”

Section: Methodsmentioning

confidence: 99%

“…Primer sequences are published or available on request [5, 9]. For the statistical analysis, significant outliers were determined using a Grubbs test (GraphPad software) and excluded.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Thyroid Hormones and Derivatives: Endogenous Thyroid Hormones and Their Targets

Köhrle

2018

Methods in Molecular Biology

View full text Add to dashboard Cite

More than a century after the discovery of L-Thyroxine, the main thyroid hormone secreted solely by the thyroid gland, several metabolites of this iodinated, tyrosine-derived ancestral hormone have been identified. These are utilized as hormones during development, differentiation, metamorphosis, and regulation of most biochemical reactions in vertebrates and their precursor species. Among those metabolites are the thyromimetically active 3,3',5-Triiodo-L-thyronine (T3) and 3,5-Diiodo-L-thronine, reverse-T3 (3,3',5'-Triiodo-L-thyronine) with still unclear function, the recently re-discovered thyronamines (e.g., 3-Iodo-thyronamine), which exert in part T3-antagonistic functions, the thyroacetic acids (e.g., Tetrac and Triac), as well as various sulfated or glucuronidated metabolites of this panel of iodinated signaling compounds. In the blood most of these hydrophobic metabolites are tightly bound to the serum distributor proteins thyroxine binding globulin (TBG), transthyretin (TTR), albumin or apolipoprotein B100. Cellular import and export of these charged, highly hydrophobic amino acid derivatives requires a number of cell-membrane transporters or facilitators such as MCT8 or MCT10 and members of the OATP and LAT families of transporters. Depending on their structure, the thyroid hormone metabolites exert their cellular action by binding and thus modulating the function of various receptors systems (e.g., ανβ3 integrin receptor and transient receptor potential channels (TRPM8) of the cell membrane), in part linked to intracellular downstream kinase signaling cascades, and several isoforms of membrane-associated, mitochondrial or nuclear thyroid hormone receptors (TR), which are members of the c-erbA family of ligand-modulated transcription factors. Intracellular deiodinase selenoenzymes, which obligatory are membrane integrated enzymes, ornithine decarboxylase and monoamine oxidases control local availability of biologically active thyroid hormone metabolites. Inactivation of thyroid hormone metabolites occurs mainly by deiodination, sulfation or glucuronidation, reactions which favor their renal or fecal elimination.

show abstract