Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases

Masini-Repiso, Ana M.; Bonaterra, Mónica; Spitale, Luis Santos; Fulvio, Mauricio Di; Bonino, Marı́a I; Coleoni, Aldo H.; Orgnero-Gaisán, Elsa

doi:10.1016/j.humpath.2003.03.001

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…As TA1 is generated by oxidative deamination (by constitutive MAO activity) and/or deiodination of amine derivatives of thyroid hormone metabolites, the intracellular bioavailability of T3 potentially represents the limiting step in TA1 formation. Furthermore, endogenous levels were TA1 are strain‐specific and would be expected to be modified under conditions of overexpression or pharmacological inhibition of the enzymes involved in its biosynthesis (Pino et al ., ; Metszaros et al ., ; Masini‐Repiso et al ., ; Petrovic et al ., ). The consequences of each of these circumstances on the pharmacological effects of TA1 are not known and represent a potential topic of research interest.…”

Section: Discussionmentioning

confidence: 97%

Histamine mediates behavioural and metabolic effects of 3‐iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

Musilli

Siena

Manni

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSE3-Iodothyroacetic acid (TA1) is an end product of thyroid hormone metabolism. So far, it is not known if TA1 is present in mouse brain and if it has any pharmacological effects. EXPERIMENTAL APPROACHTA1 levels in mouse brain were measured by HPLC coupled to mass spectrometry. After i.c.v. administration of exogenous TA1 (0.4, 1.32 and 4 μg·kg −1 ) to mice, memory acquisition-retention (passive avoidance paradigm with a light-dark box), pain threshold to thermal stimulus (51.5°C; hot plate test) and plasma glucose (glucorefractometer) were evaluated. Similar assays were performed in mice pretreated with s.c. injections of the histamine H1 receptor antagonist pyrilamine (10 mg·kg ) and the corresponding WT strain. KEY RESULTSTA1 was found in the brain of CD1 but not of HDC mice. Exogenous TA1 induced amnesia (at 0.4 μg·kg ). All these effects were modulated by pyrilamine and zolantidine. In HDC −/− mice, TA1 (1.32 and 4 μg·kg −1) did not increase plasma glucose or induce hyperalgesia. CONCLUSIONS AND IMPLICATIONSBehavioural and metabolic effects of TA1 disclosed interactions between the thyroid and histaminergic systems. AbbreviationsT3, tri-iodothyronine; TA1, 3-iodothyroacetic acid; TA1M, 3-iodothyronamine; TRIAC, tri-iodothyroacetic acid

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Section: Discussionmentioning

confidence: 97%

Histamine mediates behavioural and metabolic effects of 3‐iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

Musilli

Siena

Manni

et al. 2014

British J Pharmacology

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“…De Micco determined that anti-TPO antibody MoAb47 recognized TPO expression in normal and benign thyroid tissues, but only in 3 % of malignant tumors [ 7 ]. TPO gene and protein expression in thyroid carcinoma have been analyzed, indicating low enzymatic activity [ 2 ], impaired solubility and suppressed TPO mRNA expression [ 8 ]. Savin et al studied the value of TPO combined with galectine-3 in DTC, observing that TPO had an intense expression in normal or hyperplasic thyroid tissue, and was down-regulated in thyroid pathologies.…”

Section: Introductionmentioning

confidence: 99%

The value of thyroperoxidase as a prognostic factor for differentiated thyroid cancer -- a long-term follow-up study

et al. 2015

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BackgroundThyroperoxidase (TPO) is a membrane-bound protein essential for the production of thyroid hormones; because of this, TPO expression may be impaired in selected thyroid diseases. The goal of this study is to analyze TPO immune expression in differentiated thyroid cancer, and to determine whether TPO has any prognostic value.MethodsA total of 139 patients who required surgery due to a thyroid nodule with signs or symptoms suspicious for malignancy during their physical, ultrasound and/or cytology examination were consecutively selected for the study. A study of TPO immunohistochemical expression was carried out on these patients using the MoAb47 monoclonal antibody. In addition, cell proliferation marker Ki67 and tumor suppressor p53 were also measured for comparison.ResultsA total of 139 cases, 43 benign tumors, 42 papillary carcinomas, 38 follicular carcinomas, 8 undifferentiated carcinomas, and 8 sporadic medullary carcinomas were analyzed. The relationship between TPO expression and disease was statistically significant (p <0.001), and decreased with tumor dedifferentiation extent. Increased TPO expression in benign lesions as compared to decreased expression in papillary carcinomas and undifferentiated tumors is outstanding. Differences in TPO expression were observed in minimally invasive follicular carcinoma (MIFC) compared to widely invasive follicular carcinoma (WIFC). TPO expression decreases in undifferentiated malignancies in contrast with p53 and Ki67 expression, which increases in that setting. TPO, p53 and Ki67 expression was significantly related to TNM stage (p <0.001). Survival rate was 72 % after a 20-year follow-up, and 100 % for subjects with higher TPO expression.ConclusionsTPO may be useful in confirming or ruling out benign diseases from differentiated thyroid carcinoma, with the exception of low-risk carcinoma such as MIFC. It could be used as a prognostic factor for differentiated thyroid cancer and patient follow-up, together with other markers.

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“…Furthermore, the fact that in the thyroid a very high mitochondrial MAO-A, and low MAO-B, is present ( 22 ) might account for the long half-life of the amine in the gland.…”

Section: T1am Pharmacokineticmentioning

confidence: 99%

Central Effects of 3-Iodothyronamine Reveal a Novel Role for Mitochondrial Monoamine Oxidases

2018

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3-Iodothyronamine (T1AM) is the last iodinated thyronamine generated from thyroid hormone alternative metabolism found circulating in rodents and in humans. So far, the physiopathological meaning of T1AM tissue levels is unknown. Much is instead known on T1AM pharmacological effects in rodents. Such evidence indicates that T1AM acutely modifies, with high potency and effectiveness, rodents’ metabolism and behavior, often showing inverted U-shaped dose–response curves. Although several possible targets for T1AM were identified, the mechanism underlying T1AM behavioral effects remains still elusive. T1AM pharmacokinetic features clearly indicate the central nervous system is not a preferential site for T1AM distribution but it is a site where T1AM levels are critically regulated, as it occurs for neuromodulators or neurotransmitters. We here summarize and discuss evidence supporting the hypothesis that central effects of T1AM derive from activation of intracellular and possibly extracellular pathways. In this respect, consisting evidence indicates the intracellular pathway is mediated by the product of T1AM phase-I non-microsomal oxidation, the 3-iodothryoacetic acid, while other data indicate a role for the trace amine-associated receptor, isoform 1, as membrane target of T1AM (extracellular pathway). Overall, these evidence might sustain the non-linear dose–effect curves typically observed when increasing T1AM doses are administered and reveal an interesting and yet unexplored link between thyroid, monoamine oxidases activity and histamine.

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Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases

Cited by 9 publications

References 31 publications

Histamine mediates behavioural and metabolic effects of 3‐iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

Histamine mediates behavioural and metabolic effects of 3‐iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

The value of thyroperoxidase as a prognostic factor for differentiated thyroid cancer -- a long-term follow-up study

Central Effects of 3-Iodothyronamine Reveal a Novel Role for Mitochondrial Monoamine Oxidases

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