Chemistry and Biology of Thyrotropin-Releasing Hormone (TRH) and its Analogs

Monga, Vikramdeep; Meena, Chhuttan Lal; Kaur, Navneet; Jain, Rahul

doi:10.2174/092986708786242912

Cited by 51 publications

(75 citation statements)

References 109 publications

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“…Administration of thyrotropin-releasing hormone (TRH) (pyroglutamyl-histidyl-prolinamide; pGlu-His-ProNH 2 ) causes many CNS effects in rodents, including reversal of sedation induced by narcotics ('arousal'), reduction in pain sensitivity (antinociception), and decreased depression-like behaviors (for review, see (Monga et al, 2008)). Many TRH analogs were synthesized that exhibited improved CNS activity (for review, see (Kinoshita et al, 1998)).…”

Section: Introductionmentioning

confidence: 99%

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thirunarayanan

Nir

Raaka

et al. 2012

Neuropsychopharmacol

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Thyrotropin-releasing hormone receptor type 2 (TRH-R2), not TRH-R1, has been proposed to mediate the CNS effects of TRH and its more effective analog taltirelin (TAL). Consistent with this idea, TAL exhibited higher binding affinity and signaling potency at mouse TRH-R2 than TRH-R1 in a model cell system. We used TRH-R1 knockout (R1ko), R2ko and R1/R2ko mice to determine which receptor mediates the CNS effects of TAL. There was no TRH-R1 mRNA in R1ko and R1/R2ko mice and no TRH-R2 mRNA in R2ko and R1/R2ko mice. Specific [ 3 H]MeTRH binding to whole brain membranes was 5% of wild type (WT) for R1ko mice, 100% for R2ko mice and 0% for R1/R2ko mice, indicating TRH-R1 is the predominant receptor expressed in the brain. In arousal assays, TAL shortened sleep time with pentobarbital sedation in WT and R2ko mice by 44 and 49% and with ketamine/xylazine sedation by 66 and 55%, but had no effect in R1ko and R1/R2ko mice. In a tail flick assay of nociception, TAL increased response latency by 65 and 70% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. In a tail suspension test of depression-like behavior, TAL increased mobility time by 49 and 37% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. Thus, in contrast to the generally accepted view that the CNS effects of TAL are mediated by TRH-R2, these effects are mediated primarily if not exclusively by TRH-R1 in mice. Neuropsychopharmacology (2013) 38, 950-956;

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Section: Introductionmentioning

confidence: 99%

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thirunarayanan

Nir

Raaka

et al. 2012

Neuropsychopharmacol

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“…norepinephrine, adrenaline, dopamine, neuropeptide Y, opioids, glutamate, GABA) [9][10][11]53]. The TRH half-life in plasma is rather short and ranges from 2 to 6 min in both animals and humans [34]. The rapid degradation of TRH after release from cells is the main factor limiting its potential use as a therapeutic agent.…”

Section: Trh -Biosynthesis Metabolism Distribution and Intracellulamentioning

confidence: 99%

“…The rapid degradation of TRH after release from cells is the main factor limiting its potential use as a therapeutic agent. Specific proteolytic enzymes which act on TRH can be found in many tissues, including brain, spinal cord, pituitary, liver, kidney, pancreas, adrenal glands and blood [11,34]. Tyreoliberinases (histydylproline imidopeptidases) are mainly responsible for TRH degradation in blood, while pyroglutamyl endopeptidases (PPI and PPII) and propyl endopeptidase act mainly in the CNS.…”

Section: Trh -Biosynthesis Metabolism Distribution and Intracellulamentioning

confidence: 99%

“…Tyreoliberinases (histydylproline imidopeptidases) are mainly responsible for TRH degradation in blood, while pyroglutamyl endopeptidases (PPI and PPII) and propyl endopeptidase act mainly in the CNS. A result of the action of TRH metabolizing enzymes is the generation of physiologically active substances like stable cyclized metabolite CHP (histydyl-proline-diketopiperizine) and deamidated free acid, TRH-OH [11,34] TRH appears to initiate its biological activity by binding with high affinity to the cell membrane of thyrotropin releasing hormone receptors (TRH-R) (Fig. 1).…”

Section: Trh -Biosynthesis Metabolism Distribution and Intracellulamentioning

confidence: 99%

“…PLC hydrolyzes the phosphoinositols of the cell membrane (phosphatydyl-inositol -PI, phosphatydylinositol-3-phosphate -PIP, phosphatydyl-inositol-4,5-diphosphate -PIP 2 ) and generates secondary messengers such as diacyloglicerol (DAG) and inositol- ( [46]. There is widespread distribution of TRH receptors in the brain with the highest occurrence in the limbic regions (hypothalamus, amygdala) and the lowest in the brain stem and cerebellum [11,34].…”

Section: Trh -Biosynthesis Metabolism Distribution and Intracellulamentioning

confidence: 99%

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Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Jantas¹

2010

Advances in Cell Biology

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Summary:The physiological role of thyreoliberin (TRH) is the preservation of homeostasis within four systems (i) the hypothalamic-hypophsysiotropic neuroendocrine system, (ii) the brain stem/midbrain/spinal cord system, (iii) the limbic/cortical system, and (iv) the chronobiological system. Thus TRH, via various cellular mechanisms, regulates a wide range of biological processes (arousal, sleep, learning, locomotive activity, mood) and possesses the potential for unique and widespread applications for treatment of human illnesses. Since the therapeutic potential of TRH is limited by its pharmacological profile (enzymatic instability, short half-life, undesirable effects), several synthetic analogues of TRH were constructed and studied in mono-or adjunct therapy of central nervous system (CNS) disturbances. The present article summarizes the current state of understanding of the physiological role of TRH and describes its putative role in clinical indications in CNS maladies with a focus on the action of TRH analogues.

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Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

Sandow

2013

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Hypothalamic and Pituitary Hormones 2.1. The Hypothalamic–Pituitary System 2.2. Pituitary Hormone Preparations 2.2.1. Thyrotropin‐Releasing Hormone (TRH) 2.2.2. Thyrotropin (TSH) 2.2.3. Luteinizing Hormone Releasing Hormone (LHRH, GnRH) 2.2.4. Luteinizing Hormone (LH), Follitropin (FSH), Human Chorionic Gonadotropin (HCG) 2.3. Growth Hormone and Prolactin Regulation 2.3.1. Growth‐Hormone‐Releasing Hormone 2.3.2. Somatostatin 2.3.3. Growth Hormone 2.3.4. Prolactin and Human Placental Lactogen (HPL) 2.4. The Melanocortin System 2.4.1. Corticotropin‐Releasing Hormone (CRH) 2.4.2. Corticotropin (ACTH) 2.4.3. Melanocyte‐Stimulating Hormone (MSH) 2.4.4. Melanocortins 2.4.5. Proopiomelanocortin (POMC) Processing 2.5. New Hypothalamic–Pituitary Peptides 2.6. Neurohypophyseal Peptides 2.6.1. Vasopressin 2.6.2. Oxytocin 3. Calcium‐Regulating Hormones 3.1. Calcitonin 3.2. Parathormone

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Chemistry and Biology of Thyrotropin-Releasing Hormone (TRH) and its Analogs

Cited by 51 publications

References 109 publications

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

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