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Thomas S. Scanlan - One of the best experts on this subject based on the ideXlab platform.

  • effects of acute microinjections of the Thyroid Hormone Derivative 3 iodothyronamine to the preoptic region of adult male rats on sleep thermoregulation and motor activity
    Hormones and Behavior, 2013
    Co-Authors: Thomas D James, Thomas S. Scanlan, Steven X Moffett, Joseph V Martin
    Abstract:

    Abstract The decarboxylated Thyroid Hormone Derivative 3-iodothyronamine (T1AM) has been reported as having behavioral and physiological consequences distinct from those of Thyroid Hormones. Here, we investigate the effects of T1AM on EEG-defined sleep after acute administration to the preoptic region of adult male rats. Our laboratory recently demonstrated a decrease in EEG-defined sleep after administration of 3,3′,5-triiodo- l -thyronine (T3) to the same brain region. After injection of T1AM or vehicle solution, EEG, EMG, activity, and core body temperature were recorded for 24 h. Sleep parameters were determined from EEG and EMG data. Earlier investigations found contrasting systemic effects of T3 and T1AM, such as decreased heart rate and body temperature after intraperitoneal T1AM injection. However, nREM sleep was decreased in the present study after injections of 1 or 3 μg T1AM, but not after 0.3 or 10 μg, closely mimicking the previously reported effects of T3 administration to the preoptic region. The biphasic dose–response observed after either T1AM or T3 administration seems to indicate shared mechanisms and/or functions of sleep regulation in the preoptic region. Consistent with systemic administration of T1AM, however, microinjection of T1AM decreased body temperature. The current study is the first to show modulation of sleep by T1AM, and suggests that T1AM and T3 have both shared and independent effects in the adult mammalian brain.

  • Biosynthesis of 3-iodothyronamine (T1AM) is dependent on the sodium-iodide symporter and thyroperoxidase but does not involve extraThyroidal metabolism of T4.
    Endocrinology, 2012
    Co-Authors: Sarah A. Hackenmueller, Riccardo Zucchi, Maja Marchini, Alessandro Saba, Thomas S. Scanlan
    Abstract:

    3-Iodothyronamine (T1AM) is an endogenous Thyroid Hormone Derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T1AM is an extraThyroidal metabolite of T4. This study uses an isotope-labeled T4 [heavy-T4 (H-T4)] that can be distinguished from endogenous T4 by mass spectrometry, which allows metabolites to be identified based on the presence of this unique isotope signature. Endogenous T1AM levels depend upon Thyroid status and decrease upon induction of hypoThyroidism. However, in hypoThyroid mice replaced with H-T4, the isotope-labeled H-T3 metabolite is detected, but no isotope-labeled T1AM is detected. These data suggest that T1AM is not an extraThyroidal metabolite of T4, yet is produced by a process that requires the same biosynthetic factors necessary for T4 synthesis.

  • Transport of Thyroid Hormones is selectively inhibited by 3-iodothyronamine
    Molecular BioSystems, 2010
    Co-Authors: Alexandra G Ianculescu, Theo J. Visser, Edith C. H. Friesema, Kathleen M. Giacomini, Thomas S. Scanlan
    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.

  • 3-Iodothyronamine (T1AM): a new chapter of Thyroid Hormone endocrinology?
    Molecular BioSystems, 2010
    Co-Authors: Alexandra G Ianculescu, Thomas S. Scanlan
    Abstract:

    3-Iodothyronamine (T1AM) is an endogenous Thyroid Hormone Derivative with distinct biological effects that are largely opposite those of Thyroid Hormone. Administration of T1AM to rodents results in rapid and profound reduction in body temperature, heart rate, and metabolism. The structural similarities between thyroxine, T1AM, and monoamine neurotransmitters suggest an intriguing role for T1AM as both a neuromodulator and a Hormone-like molecule that may constitute a part of Thyroid Hormone action. Several recent studies into its molecular mechanisms of action have shown that T1AM can target extracellular receptors such as the trace amine-associated receptors and the α2A adrenergic receptor, modulate the membrane transport of neurotransmitters, and serve as a substrate of specific membrane transport cellular uptake machinery. This review discusses recent T1AM studies, focusing on both the observed in vivo effects of T1AM administration and its actions at the molecular level.

  • 3-Iodothyronamine (T(1)AM): a new chapter of Thyroid Hormone endocrinology?
    Molecular bioSystems, 2010
    Co-Authors: Alexandra G Ianculescu, Thomas S. Scanlan
    Abstract:

    3-Iodothyronamine (T(1)AM) is an endogenous Thyroid Hormone Derivative with distinct biological effects that are largely opposite those of Thyroid Hormone. Administration of T(1)AM to rodents results in rapid and profound reduction in body temperature, heart rate, and metabolism. The structural similarities between thyroxine, T(1)AM, and monoamine neurotransmitters suggest an intriguing role for T(1)AM as both a neuromodulator and a Hormone-like molecule that may constitute a part of Thyroid Hormone action. Several recent studies into its molecular mechanisms of action have shown that T(1)AM can target extracellular receptors such as the trace amine-associated receptors and the alpha(2A) adrenergic receptor, modulate the membrane transport of neurotransmitters, and serve as a substrate of specific membrane transport cellular uptake machinery. This review discusses recent T(1)AM studies, focusing on both the observed in vivo effects of T(1)AM administration and its actions at the molecular level.

J. N. Scutt - One of the best experts on this subject based on the ideXlab platform.

  • the Thyroid Hormone Derivative 3 iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, N. A. Patel, J. N. Scutt, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, Kevin Murphy, Alan Armstrong
    Abstract:

    Background:  The Thyroid Hormone Derivative 3-iodothyronamine (T1AM), an endogenous biogenic amine, is a potent agonist of the G protein–coupled trace amine-associated receptor 1 (TAAR1). T1AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. Aim:  The aim of this study was to determine the effects of T1AM on food intake in rodents. Methods:  We determined the effect of (i) intraperitoneal (i.p.) administration of T1AM on food intake, oxygen consumption (VO2) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T1AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T1AM in male rats; and (iv) direct injection of T1AM into the arcuate nucleus (ARC) of male rats on food intake. Results:  (i) T1AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO2 or locomotor activity. (ii) ICV administration of T1AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T1AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T1AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. Conclusion:  These data suggest that T1AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

  • The Thyroid Hormone Derivative 3-iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, K. G. Murphy, N. A. Patel, D. Roy, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, J. N. Scutt
    Abstract:

    BACKGROUND: The Thyroid Hormone Derivative 3-iodothyronamine (T(1)AM), an endogenous biogenic amine, is a potent agonist of the G protein-coupled trace amine-associated receptor 1 (TAAR1). T(1)AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. AIM: The aim of this study was to determine the effects of T(1)AM on food intake in rodents. METHODS: We determined the effect of (i) intraperitoneal (i.p.) administration of T(1)AM on food intake, oxygen consumption (VO(2)) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T(1)AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T(1)AM in male rats; and (iv) direct injection of T(1)AM into the arcuate nucleus (ARC) of male rats on food intake. RESULTS: (i) T(1)AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO(2) or locomotor activity. (ii) ICV administration of T(1)AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T(1)AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T(1)AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. CONCLUSION: These data suggest that T(1)AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

Waljit S. Dhillo - One of the best experts on this subject based on the ideXlab platform.

  • the Thyroid Hormone Derivative 3 iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, N. A. Patel, J. N. Scutt, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, Kevin Murphy, Alan Armstrong
    Abstract:

    Background:  The Thyroid Hormone Derivative 3-iodothyronamine (T1AM), an endogenous biogenic amine, is a potent agonist of the G protein–coupled trace amine-associated receptor 1 (TAAR1). T1AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. Aim:  The aim of this study was to determine the effects of T1AM on food intake in rodents. Methods:  We determined the effect of (i) intraperitoneal (i.p.) administration of T1AM on food intake, oxygen consumption (VO2) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T1AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T1AM in male rats; and (iv) direct injection of T1AM into the arcuate nucleus (ARC) of male rats on food intake. Results:  (i) T1AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO2 or locomotor activity. (ii) ICV administration of T1AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T1AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T1AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. Conclusion:  These data suggest that T1AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

  • The Thyroid Hormone Derivative 3-iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, K. G. Murphy, N. A. Patel, D. Roy, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, J. N. Scutt
    Abstract:

    BACKGROUND: The Thyroid Hormone Derivative 3-iodothyronamine (T(1)AM), an endogenous biogenic amine, is a potent agonist of the G protein-coupled trace amine-associated receptor 1 (TAAR1). T(1)AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. AIM: The aim of this study was to determine the effects of T(1)AM on food intake in rodents. METHODS: We determined the effect of (i) intraperitoneal (i.p.) administration of T(1)AM on food intake, oxygen consumption (VO(2)) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T(1)AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T(1)AM in male rats; and (iv) direct injection of T(1)AM into the arcuate nucleus (ARC) of male rats on food intake. RESULTS: (i) T(1)AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO(2) or locomotor activity. (ii) ICV administration of T(1)AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T(1)AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T(1)AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. CONCLUSION: These data suggest that T(1)AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

Alan Armstrong - One of the best experts on this subject based on the ideXlab platform.

  • the Thyroid Hormone Derivative 3 iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, N. A. Patel, J. N. Scutt, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, Kevin Murphy, Alan Armstrong
    Abstract:

    Background:  The Thyroid Hormone Derivative 3-iodothyronamine (T1AM), an endogenous biogenic amine, is a potent agonist of the G protein–coupled trace amine-associated receptor 1 (TAAR1). T1AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. Aim:  The aim of this study was to determine the effects of T1AM on food intake in rodents. Methods:  We determined the effect of (i) intraperitoneal (i.p.) administration of T1AM on food intake, oxygen consumption (VO2) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T1AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T1AM in male rats; and (iv) direct injection of T1AM into the arcuate nucleus (ARC) of male rats on food intake. Results:  (i) T1AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO2 or locomotor activity. (ii) ICV administration of T1AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T1AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T1AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. Conclusion:  These data suggest that T1AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

J. V. Gardiner - One of the best experts on this subject based on the ideXlab platform.

  • the Thyroid Hormone Derivative 3 iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, N. A. Patel, J. N. Scutt, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, Kevin Murphy, Alan Armstrong
    Abstract:

    Background:  The Thyroid Hormone Derivative 3-iodothyronamine (T1AM), an endogenous biogenic amine, is a potent agonist of the G protein–coupled trace amine-associated receptor 1 (TAAR1). T1AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. Aim:  The aim of this study was to determine the effects of T1AM on food intake in rodents. Methods:  We determined the effect of (i) intraperitoneal (i.p.) administration of T1AM on food intake, oxygen consumption (VO2) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T1AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T1AM in male rats; and (iv) direct injection of T1AM into the arcuate nucleus (ARC) of male rats on food intake. Results:  (i) T1AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO2 or locomotor activity. (ii) ICV administration of T1AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T1AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T1AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. Conclusion:  These data suggest that T1AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.

  • The Thyroid Hormone Derivative 3-iodothyronamine increases food intake in rodents
    Diabetes Obesity and Metabolism, 2009
    Co-Authors: Waljit S. Dhillo, J. V. Gardiner, K. G. Murphy, N. A. Patel, D. Roy, A. Bataveljic, Gavin A Bewick, E L Thompson, N. E. White, J. N. Scutt
    Abstract:

    BACKGROUND: The Thyroid Hormone Derivative 3-iodothyronamine (T(1)AM), an endogenous biogenic amine, is a potent agonist of the G protein-coupled trace amine-associated receptor 1 (TAAR1). T(1)AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis. AIM: The aim of this study was to determine the effects of T(1)AM on food intake in rodents. METHODS: We determined the effect of (i) intraperitoneal (i.p.) administration of T(1)AM on food intake, oxygen consumption (VO(2)) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T(1)AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T(1)AM in male rats; and (iv) direct injection of T(1)AM into the arcuate nucleus (ARC) of male rats on food intake. RESULTS: (i) T(1)AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO(2) or locomotor activity. (ii) ICV administration of T(1)AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T(1)AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T(1)AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake. CONCLUSION: These data suggest that T(1)AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.