Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3β inhibitor

Pekary, A. Eugene; Stevens, Schetema A.; Blood, James; Sattin, Albert

doi:10.1016/j.peptides.2010.03.020

Cited by 12 publications

(9 citation statements)

References 59 publications

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“…Withdrawal of RF resulted in significant decreases in the levels of all TRH and TRH-like peptides measured in the adrenals (Table 3 ). This is consistent with an acute decrease in biosynthesis and/or increase in release of these peptides [ 32 ]. RF has modest, transient, and beneficial effects on stress-related changes in the gut microbiome, inflammation, permeability and hyperalgesia as well as central responses to social stress [ 15 , 17 , 18 , 42 ].…”

Section: Discussionsupporting

confidence: 82%

“…These changes result from alterations in the biosynthesis and release of these tripeptides. The rapidity of these responses is consistent with increased TRH, Val-TRH, Phe-TRH and Trp-TRH and decreased Tyr-TRH release, respectively [ 32 ]. These remarkable changes in peptide levels within the MED is consistent with current knowledge regarding the role of TRH (and TRH-like peptides) as mediators of brain-gut communication via the vagus nerve [ 10 , 36 ].…”

Section: Discussionmentioning

confidence: 67%

“…The antidepressant activity of Tyr-TRH [ 31 ] and analeptic effect of Val-TRH [ 37 ] correspond with actions of TRH [ 11 ]. TRH and TRH-like peptide biosynthesis occurs within large dense core vesicles (LDCV) of glutamatergic neurons [ 32 , 33 ]. They are co-released with glutamate and act to moderate the effects of this excitotoxic neurotransmitter [ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

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Rifaximin modulates TRH and TRH-like peptide expression throughout the brain and peripheral tissues of male rats

Pekary

Sattin

2022

BMC Neurosci

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Background The TRH/TRH-R1 receptor signaling pathway within the neurons of the dorsal vagal complex is an important mediator of the brain-gut axis. Mental health and protection from a variety of neuropathologies, such as autism, Attention Deficit Hyperactivity Disorder, Alzheimer’s and Parkinson’s disease, major depression, migraine and epilepsy are influenced by the gut microbiome and is mediated by the vagus nerve. The antibiotic rifaximin (RF) does not cross the gut-blood barrier. It changes the composition of the gut microbiome resulting in therapeutic benefits for traveler’s diarrhea, hepatic encephalopathy, and prostatitis. TRH and TRH-like peptides, with the structure pGlu-X-Pro-NH2, where “X” can be any amino acid residue, have reproduction-enhancing, caloric-restriction-like, anti-aging, pancreatic-β cell-, cardiovascular-, and neuroprotective effects. TRH and TRH-like peptides occur not only throughout the CNS but also in peripheral tissues. To elucidate the involvement of TRH-like peptides in brain-gut-reproductive system interactions 16 male Sprague–Dawley rats, 203 ± 6 g, were divided into 4 groups (n = 4/group): the control (CON) group remained on ad libitum Purina rodent chow and water for 10 days until decapitation, acute (AC) group receiving 150 mg RF/kg powdered rodent chow for 24 h providing 150 mg RF/kg body weight for 200 g rats, chronic (CHR) animals receiving RF for 10 days; withdrawal (WD) rats receiving RF for 8 days and then normal chow for 2 days. Results Significant changes in the levels of TRH and TRH-like peptides occurred throughout the brain and peripheral tissues in response to RF. The number of significant changes in TRH and TRH-like peptide levels in brain resulting from RF treatment, in descending order were: medulla (16), piriform cortex (8), nucleus accumbens (7), frontal cortex (5), striatum (3), amygdala (3), entorhinal cortex (3), anterior (2), and posterior cingulate (2), hippocampus (1), hypothalamus (0) and cerebellum (0). The corresponding ranking for peripheral tissues were: prostate (6), adrenals (4), pancreas (3), liver (2), testis (1), heart (0). Conclusions The sensitivity of TRH and TRH-like peptide expression to RF treatment, particularly in the medulla oblongata and prostate, is consistent with the participation of these peptides in the therapeutic effects of RF.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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Rifaximin modulates TRH and TRH-like peptide expression throughout the brain and peripheral tissues of male rats

Pekary

Sattin

2022

BMC Neurosci

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“…TRH microinjected into the SCN between 4 and 8 h, but not at other times, can phase shift running wheel activity [31]. Acute decline in levels of TRH-like peptides during the dark/high-activity phase can be attributed to increased release/clearance from glutamatergic neuron and other TRH-like peptide containing cells [1,32].…”

Section: Introductionmentioning

confidence: 99%

TRH and TRH-Like Peptide Levels Co-Vary with Reproductive and Metabolic Rhythms

Pekary

Sattin

2016

Horm Metab Res

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Photoperiod-synchronized rhythms in non-CSN tissues persist in total darkness. Clock genes involved in maintaining regular biorhythms within the suprachiasmatic nucleus (SCN) of the hypothalamus are expressed in extra-CNS tissues and continue periodic expression in vitro. Understanding the details of how the SCN clock is coupled with peripheral clocks is only incompletely understood and may involve a multiplicity of feedback systems. The present study is an extension of our previous work showing that brain levels of TRH (pGlu-His-Pro-NH) and TRH-like peptides (X-TRH: pGlu-X-Pro-NH, where "X" can be any amino acid residue) fluctuate throughout the day-night cycle. Male rats were maintained in a stable environment, lights on 6-18 h. TRH and TRH-like peptides in liver, pancreas, testis, prostate, epididymis, and heart were measured at 3, 10, 16, and 22 h. The greatest change in peptide level was a 12-fold increase for TRH in prostate at 16 h relative to the corresponding value at 3 h. The TRH, Tyr-TRH and Phe-TRH levels in liver declined steadily to about 40% of the 3-h values by 22 h. Changes, in the order of decreasing number of significant increases (↑) and/or decreases (↓), were: testis (5↑, 1↓), liver (3↓), epididymis (2↑), prostate (1↑, 1↓) and heart (1↑). Peptide levels in liver and testis correlated with serum leptin and serum corticosterone, respectively, which are potent releasers of these peptides. Testosterone and glucose were also highly correlated. These tripeptides may participate in the regulation of metabolic and reproductive functions, which change during the day-night cycle.

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“…GSK3 beta ekspresyonunu azaltmaktadır(37). İUB'nin manik fazında artan GSK3 beta aktivitesi, TRH'yi baskılayarak, reaktif bir şekilde serbest T4 artışına yol açıyor olabilir.Sonuç olarak başlangıç yaşı ileri ve aile öyküsü olmayan iki uçlu olgularda, diyabet tanısı hatırlanmalı ve araştırılmalıdır.…”

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