Thyrotropin-releasing hormone (TRH) is an important endocrine agent that regulates the function of cells in the anterior pituitary and the central and peripheral nervous systems. By controlling the synthesis and release of thyroid hormones, TRH affects many physiological functions, including energy homeostasis. This hormone exerts its effects through G protein-coupled TRH receptors, which signal primarily through Gq/11 but may also utilize other G protein classes under certain conditions. Because of the potential therapeutic benefit, considerable attention has been devoted to the synthesis of new TRH analogs that may have some advantageous properties compared with TRH. In this context, it may be interesting to consider the phenomenon of biased agonism and signaling at the TRH receptor. This possibility is supported by some recent findings. Although knowledge about the mechanisms of TRH receptor-mediated signaling has increased steadily over the past decades, there are still many unanswered questions, particularly about the molecular details of post-receptor signaling. In this review, we summarize what has been learned to date about TRH receptor-mediated signaling, including some previously undiscussed information, and point to future directions in TRH research that may offer new insights into the molecular mechanisms of TRH receptor-triggered actions and possible ways to modulate TRH receptor-mediated signaling.

• Klíčová slova
• G protein, TRH receptors, signaling, thyrotropin-releasing hormone, β-arrestin,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Metabolic interactions between adipose tissue and the heart may play an active role in progression of heart failure (HF). The aim of the study was to examine changes in myocardial and adipose tissue metabolism and gene expression in a rat HF model induced by chronic volume overload. HF was induced by volume overload from aorto-caval fistula (ACF) in 3-month-old male Wistar rats and animals were studied in the phase of decompensated HF (22nd week). HF rats showed marked eccentric cardiac hypertrophy, pulmonary congestion, increased LV end-diastolic pressure, and intraabdominal fat depletion. HF rats had preserved glucose tolerance, but increased circulating free fatty acids (FFA) and attenuated insulin response during oral glucose challenge. Isolated organ studies showed preserved responsiveness of adipose tissue lipolysis and lipogenesis to epinephrine and insulin in ACF. The heart of HF animals had markedly reduced triglyceride content (almost to half of controls), attenuated anti-oxidative reserve (GSH/GSSG), upregulated HF markers (ANP, periostin, thrombospondin-4), specific signaling pathways (Wnt, TGF-β), and downregulated enzymes of mitochondrial fatty acid oxidation, citric acid cycle, and respiratory chain. Adipose tissue transcription profiling showed upregulated receptor for gastric inhibitory polypeptide. In conclusion, ACF-induced HF model displays several deregulations of systemic metabolism. Despite elevation of systemic FFAs, myocardial triglycerides are low and insulin levels are attenuated, arguing against a role of lipotoxicity or insulin resistance in this model. Attenuated postprandial insulin response and relative lack of its antilipolytic effects may facilitate intraabdominal fat depletion observed in ACF-HF animals.

• MeSH
• aorta chirurgie   MeSH
• arteriovenózní píštěl MeSH
• arteriovenózní zkrat MeSH
• biologické markery metabolismus   MeSH
• epididymis metabolismus   patologie   MeSH
• glukózový toleranční test MeSH
• glutathion metabolismus   MeSH
• hemodynamika MeSH
• inzulin krev   MeSH
• játra patologie   MeSH
• kardiomyocyty metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné neesterifikované krev   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• ledviny patologie   MeSH
• metabolismus lipidů MeSH
• myokard metabolismus   patologie   MeSH
• oxidační stres MeSH
• plíce patologie   MeSH
• potkani Wistar MeSH
• remodelace komor MeSH
• srdce patofyziologie   MeSH
• srdeční selhání metabolismus   patologie   patofyziologie   MeSH
• stanovení celkové genové exprese MeSH
• superoxiddismutasa metabolismus   MeSH
• tuková tkáň metabolismus   patologie   MeSH
• velikost orgánu MeSH
• venae cavae chirurgie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• glutathion MeSH
• inzulin MeSH
• kyseliny mastné neesterifikované MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• superoxiddismutasa MeSH