New Atmosphere, New Vision: Gibson and Whittemore Kick Off Invest in ME Conference 2016
Mark Berry reports on Dr. Gibson's introduction and Dr. Whittemore's keynote speech, at the 11th Invest in ME International ME Conference in London.
Discuss the article on the Forums.

3-Iodothyronamine ( T1AM ) administered to rodents induce a hypometabolic state

Discussion in 'Other Health News and Research' started by pattismith, Jan 22, 2018.

  1. pattismith

    pattismith Senior Member

    Messages:
    1,070
    Likes:
    1,604
    Could T1AM induce peripheric thyroid resistance?

    Minireview: 3-Iodothyronamine (T1AM): a new player on the thyroid endocrine team?

    Scanlan TS1.
    2009
    Abstract

    3-Iodothyronamine (T(1)AM) is an endogenous compound with chemical features that are similar to thyroid hormone. T(1)AM has a carbon skeleton identical to that of T(4) and contains a single carbon-iodine bond. Theoretically, T(1)AM could be produced from T(4) by enzymatic decarboxylation and deiodination. Recent studies show that T(1)AM and higher iodinated thyronamines are subject to similar metabolic processing as iodothyronines such as T(4), suggesting a biological linkage between iodothyronines and iodothyronamines.

    In addition, single doses of T(1)AM administered to rodents induce a hypometabolic state that in certain ways resembles hibernation and is opposite to the effects of excess T(4).
    This review will discuss the latest developments on this recently discovered thyroid hormone derivative.

    Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine

    2010
    Abstract
    Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors.

    A recently discovered thyroid hormone derivative, 3-iodothyronamine (T1AM), has distinct biological effects that are opposite those of thyroid hormone.
    Here we investigate the effects of T1AM on thyroid hormone transporters using COS-1 cells transfected with the multispecific organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 1C1, as well as the specific thyroid hormone transporters MCT8 and MCT10, and show that T1AM displays differential inhibition of T3 and T4 cellular uptake by these transporters.

    T1AM inhibits T3 and T4 transport by OATP1A2 with IC50 values of 0.27 and 2.1 µM, respectively.
    T4 transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T1AM with an IC50 of 4.8 µM.
    T1AM also inhibits both T3 and T4 uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC50 values of 95 and 31 µM, respectively. By contrast, T1AM has no effect on thyroid hormone transport by OATP1B3 and MCT10.
    Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T1AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system.
     
    Last edited: Jan 22, 2018
    ScottTriGuy and cigana like this.
  2. pattismith

    pattismith Senior Member

    Messages:
    1,070
    Likes:
    1,604
  3. pattismith

    pattismith Senior Member

    Messages:
    1,070
    Likes:
    1,604
    Review ARTICLE (Only some extracts here)
    Front. Endocrinol., 31 May 2017
    Torpor: The Rise and Fall of 3-Monoiodothyronamine from Brain to Gut—From Gut to Brain?
    ...
    5. In Vitro Pharmacodynamics of T1AM

    ...
    With respect to the target profile of T1AM, α2 adrenoceptors are activated with a similar potency as noradrenaline. Neuronal membrane as well as vesicular transporters for dopamine and noradrenaline (45, 53) and all subtypes of muscarinic acetylcholine receptors (54) are functionally blocked in the micromolar or sub-micromolar range.

    Other role of Tironamines from a study quoted in the revue:
    Thyronamines inhibit plasma membrane and vesicular monoamine transport.
    Abstract
    Thyroid hormone has long been known to have important transcriptional regulatory activities. Recently, however, the presence of endogenous derivatives of thyroid hormone, thyronamines, has been reported in various mammalian tissues. These derivatives have potent in vitro activity with a class of orphan G-protein-coupled receptors, the trace amine-associated receptors, and profound in vivo effects when administered to mice.
    We report here a novel neuromodulatory role for thyronamines. In synaptosomal preparations and heterologous expression systems, thyronamines act as specific dopamine and norepinephrine reuptake inhibitors. Thyronamines also inhibit the transport of monoamines into synaptic vesicles. These observations expand the nontranscriptional role of thyroid hormone derivatives and may help to explain the pharmacological effects of thyronamines in vivo.

    7. T1AM is Claimed to be an “Endogenous” Derivative of Thyroid Hormone—But Where and How is it Made?


    7.3. T1AM Is Not Derived from Circulating Thyroxine

    7.4. Ornithine Decarboxylase—The Missing Link
    ...A breakthrough in the mysterious biological pathway regarding the formation of T1AM was that in addition to deiodinases such as DIO1, ODC is involved....

    The entire enzymatic activity necessary to produce T1AM from T4 was shown to exist in intestinal tissue of mice (74). The tissue contained the enzyme ornithine decarboxylase (ODC) that is capable of decarboxylating T4 and its deiodinated intermediates.

    7.5. Gut Microbiota, Cecotrophy, Coprophagy
    In a recent review article (16), it is proposed that for T1AM formation, T4 must enter the gut and may not be formed enzymatically elsewhere. This could indeed explain the high levels observed by some researchers in the rat liver. But this may not be the end of the story, especially considering additional important players: the gut microbiota (75). It is long known that deiodination and degradation of T4 and T3 by gut microbiota occur in the intestine of rodents (76). Moreover, when one partially decontaminates rats by feeding ampicillin, the metabolism of T4 and T3 is drastically changed (77). The intestinal wall contains ODC, but rodent gut microbes in the cecum and colon are another excellent source as Klebsiella, Pseudomonas, and E. coli (78) feature abundant constitutive and inducible (i.e., biodegradative) ODC. These enzymes appear to differ in some respect from the mammalian counterparts as the potent irreversible blocker difluoromethylornithine, currently in clinical cancer trials (79), inhibits ODCs of Pseudomonas aeruginosa but not those of Klebsiella pneumoniae and E. coli (80). Furthermore, there are enzymes in the gut microbiota of humans, and perhaps rodents, that are capable of decarboxylating aromatic amines (81). It is suggested to analyze T1AM in germ-free rats or axenic mice to refute the hypothesis about the role of gut bacteria.
    ...
     
    Last edited: Feb 5, 2018
    ScottTriGuy likes this.

See more popular forum discussions.

Share This Page