@article{MTMT:34578220,
	title = {GLP-1 Receptor Signaling Has Different Effects on the Perikarya and Axons of the Hypophysiotropic Thyrotropin-Releasing Hormone Synthesizing Neurons in Male Mice},
	url = {https://m2.mtmt.hu/api/publication/34578220},
	author = {Ruska, Yvette Magdolna and Péterfi, Zoltán Attila and Stiftné Szilvásy-Szabó, Anett and Kővári, Dóra and Hrabovszky, Erik and Dorogházi, Beáta Vanessza and Gereben, Balázs and Tóth, Blanka and Matziari, Magdalini and Wittmann, Gábor and Fekete, Csaba},
	doi = {10.1089/thy.2023.0284},
	journal-iso = {THYROID},
	journal = {THYROID},
	volume = {34},
	unique-id = {34578220},
	issn = {1050-7256},
	abstract = {Background: Glucagon-like peptide 1 (GLP-1) is involved in the regulation of energy and glucose homeostasis. As GLP-1 has similar effects on the energy homeostasis as the hypophysiotropic thyrotropin-releasing hormone (TRH) neurons that regulate the hypothalamic-pituitary-thyroid (HPT) axis, we raised the possibility that the TRH neurons are involved in the mediation of the effects of GLP-1. Therefore, the relationship and interaction of the GLP-1 system and the TRH neurons of the hypothalamic paraventricular nucleus (PVN) were studied.Methods: To examine the anatomical and functional relationship of TRH neurons and the GLP-1 system in the PVN, immunocytochemistry, in situ hybridization, in vitro patch-clamp electrophysiology, metabolic phenotyping, and explant experiments were performed.Results: Our data demonstrate that the TRH neurons of the PVN are innervated by GLP-1 producing neurons and express the GLP-1 receptor (GLP-1R). However, not only do the GLP-1-innervated TRH neurons express GLP-1R but the receptor is also present in the axons of the hypophysiotropic TRH neurons in the blood-brain barrier free median eminence (ME) suggesting that peripherally derived GLP-1 may also influence the TRH neurons. In vitro, GLP-1 increased the firing rate of TRH neurons and depolarized them. In addition, GLP-1 directly stimulated the GABAergic input of a population of TRH neurons. Furthermore, GLP-1 inhibited the release of TRH from the hypophysiotropic axons in the ME. In vivo, peripheral GLP-1R agonist administration markedly inhibited the food intake and the energy expenditure, but had no effect on the TRH expression in the PVN and resulted in lower circulating free T4 levels.Conclusions: Our results indicate that GLP-1R activation has a direct stimulatory effect on TRH neurons in the PVN, but the activation of GLP-1R may also inhibit TRH neurons by facilitating their inhibitory inputs or by inhibiting the axon terminals of these cells in the ME. The innervation of TRH neurons by GLP-1 neurons suggests that TRH neurons might be influenced by both circulating GLP-1 and by GLP-1 neurons of the nucleus tractus solitarii. The lack of GLP-1R agonist-induced regulation of TRH neurons in vivo suggests that the HPT axis does not mediate the GLP-1R agonist-induced weight loss.},
	keywords = {Release; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; median eminence; TRH; Glucagon-like peptide-1 receptor},
	year = {2024},
	eissn = {1557-9077},
	pages = {252-260},
	orcid-numbers = {Kővári, Dóra/0000-0001-5346-822X}
}

@article{MTMT:34391689,
	title = {Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism},
	url = {https://m2.mtmt.hu/api/publication/34391689},
	author = {Batistuzzo, Alice and Salas-Lucia, Federico and Gereben, Balázs and Ribeiro, Miriam O and Bianco, Antonio C},
	doi = {10.1210/endocr/bqad155},
	journal-iso = {ENDOCRINOLOGY},
	journal = {ENDOCRINOLOGY},
	volume = {164},
	unique-id = {34391689},
	issn = {0013-7227},
	abstract = {The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be “sensed” directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.},
	keywords = {feedback; PITUITARY; Thyroid; TSH; Deiodinase},
	year = {2023},
	eissn = {1945-7170},
	orcid-numbers = {Batistuzzo, Alice/0000-0003-2815-7504; Salas-Lucia, Federico/0000-0003-4141-5790; Bianco, Antonio C/0000-0001-7737-6813}
}

@article{MTMT:34232164,
	title = {In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse},
	url = {https://m2.mtmt.hu/api/publication/34232164},
	author = {Sinkó, Richárd and Mohácsik, Petra and Fekete, Csaba and Gereben, Balázs},
	doi = {10.3791/65657},
	journal-iso = {JOVE-J VIS EXP},
	journal = {JOVE-JOURNAL OF VISUALIZED EXPERIMENTS},
	volume = {2023},
	unique-id = {34232164},
	issn = {1940-087X},
	year = {2023},
	eissn = {1940-087X}
}

@article{MTMT:33917113,
	title = {Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain},
	url = {https://m2.mtmt.hu/api/publication/33917113},
	author = {Salas-Lucia, Federico and Fekete, Csaba and Sinkó, Richárd and Egri, Péter and Rada, Kristóf Róbert and Ruska, Yvette Magdolna and Gereben, Balázs and Bianco, Antonio},
	doi = {10.7554/eLife.82683},
	journal-iso = {ELIFE},
	journal = {ELIFE},
	volume = {12},
	unique-id = {33917113},
	issn = {2050-084X},
	abstract = {The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3's active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity.},
	year = {2023},
	eissn = {2050-084X},
	orcid-numbers = {Salas-Lucia, Federico/0000-0003-4141-5790; Rada, Kristóf Róbert/0000-0001-7849-5312; Bianco, Antonio/0000-0001-7737-6813}
}

@article{MTMT:33560486,
	title = {Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4)},
	url = {https://m2.mtmt.hu/api/publication/33560486},
	author = {Kozsurek, Márk and Király, Kornél P and Gyimesi, Klára and Lukácsi, Erika and Fekete, Csaba and Gereben, Balázs and Mohácsik, Petra and Helyes, Zsuzsanna and Bölcskei, Kata and Tékus, Valéria and Pap, Károly and Szűcs, Edina and Benyhe, Sándor and Imre, Timea and Szabó, Pál Tamás and Gajtkó, Andrea and Szentesiné Holló, Krisztina and Puskár, Zita},
	doi = {10.3390/ijms24020918},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33560486},
	issn = {1661-6596},
	abstract = {Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia.},
	keywords = {HYPERALGESIA; chronic pain; spinal cord; Allodynia; cocaine- and amphetamine-regulated transcript (CART) peptide; dipeptidyl-peptidase-4 (DPP4)},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Kozsurek, Márk/0000-0001-5465-2803; Király, Kornél P/0000-0002-7252-0422; Szabó, Pál Tamás/0000-0003-2260-4641}
}

@article{MTMT:33208795,
	title = {Different hypothalamic mechanisms control decreased circulating thyroid hormone levels in infection and fasting-induced Non-Thyroidal Illness Syndrome in male Thyroid Hormone Action Indicator Mice},
	url = {https://m2.mtmt.hu/api/publication/33208795},
	author = {Sinkó, Richárd and Mohácsik, Petra and Kővári, Dóra and Penksza, Veronika and Wittmann, Gábor and Borbélyné Mácsai, Lilla and Fonseca, Tatiana L and Bianco, Antonio Carlos and Fekete, Csaba and Gereben, Balázs},
	doi = {10.1089/thy.2022.0404},
	journal-iso = {THYROID},
	journal = {THYROID},
	volume = {33},
	unique-id = {33208795},
	issn = {1050-7256},
	keywords = {fasting; Non-thyroidal illness syndrome; Thyroid Hormone Action Indicator Mouse aging; hypothalamo-pituitary-thyroid axis; tissue-specific thyroid hormone action},
	year = {2023},
	eissn = {1557-9077},
	pages = {109-118},
	orcid-numbers = {Kővári, Dóra/0000-0001-5346-822X; Borbélyné Mácsai, Lilla/0000-0002-9503-6449}
}

@article{MTMT:33286458,
	title = {Tetrabromobisphenol A and Diclazuril Evoke Tissue-Specific Changes of Thyroid Hormone Signaling in Male Thyroid Hormone Action Indicator Mice},
	url = {https://m2.mtmt.hu/api/publication/33286458},
	author = {Sinkó, Richárd and Rada, Kristóf Róbert and Kollár, Anna and Mohácsik, Petra and Tenk, Miklós and Fekete, Csaba and Gereben, Balázs},
	doi = {10.3390/ijms232314782},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33286458},
	issn = {1661-6596},
	abstract = {Thyroid hormone (TH) signaling is a prerequisite of normal tissue function. Environmental pollutants with the potential to disrupt endocrine functions represent an emerging threat to human health and agricultural production. We used our Thyroid Hormone Action Indicator (THAI) mouse model to study the effects of tetrabromobisphenol A (TBBPA; 150 mg/bwkg/day orally for 6 days) and diclazuril (10.0 mg/bwkg/day orally for 5 days), a known and a potential hormone disruptor, respectively, on local TH economy. Tissue-specific changes of TH action were assessed in 90-day-old THAI mice by measuring the expression of a TH-responsive luciferase reporter in tissue samples and by in vivo imaging (14-day-long treatment accompanied with imaging on day 7, 14 and 21 from the first day of treatment) in live THAI mice. This was followed by promoter assays to elucidate the mechanism of the observed effects. TBBPA and diclazuril impacted TH action differently and tissue-specifically. TBBPA disrupted TH signaling in the bone and small intestine and impaired the global TH economy by decreasing the circulating free T4 levels. In the promoter assays, TBBPA showed a direct stimulatory effect on the hdio3 promoter, indicating a potential mechanism for silencing TH action. In contrast, diclazuril acted as a stimulator of TH action in the liver, skeletal muscle and brown adipose tissue without affecting the Hypothalamo-Pituitary-Thyroid axis. Our data demonstrate distinct and tissue-specific effects of TBBPA and diclazuril on local TH action and prove that the THAI mouse is a novel mammalian model to identify TH disruptors and their tissue-specific effects.},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Rada, Kristóf Róbert/0000-0001-7849-5312}
}

@article{MTMT:33128893,
	title = {Origin of thyrotropin-releasing hormone neurons that innervate the tuberomammillary nuclei},
	url = {https://m2.mtmt.hu/api/publication/33128893},
	author = {Sánchez-Jaramillo, Edith and Wittmann, Gábor and Menyhért, Judit and Singru, Praful and Gómez-González, Gabriela B. and Sánchez-Islas, Eduardo and Yáñez-Recendis, Nashiely and Pimentel-Cabrera, Jaime Arturo and León-Olea, Martha and Gereben, Balázs and Fekete, Csaba and Charli, Jean-Louis and Lechan, Ronald M.},
	doi = {10.1007/s00429-022-02527-5},
	journal-iso = {BRAIN STRUCT FUNC},
	journal = {BRAIN STRUCTURE & FUNCTION},
	volume = {227},
	unique-id = {33128893},
	issn = {1863-2653},
	abstract = {Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons function as metabolic sensors that regulate the thyroid axis and energy homeostasis. Less is known about the role of other hypothalamic TRH neurons. As central administration of TRH decreases food intake and increases histamine in the tuberomammillary nuclei (TMN), and TMN histamine neurons are densely innervated by TRH fibers from an unknown origin, we mapped the location of TRH neurons that project to the TMN. The retrograde tracer, cholera toxin B subunit (CTB), was injected into the TMN E1–E2, E4–E5 subdivisions of adult Sprague–Dawley male rats. TMN projecting neurons were observed in the septum, preoptic area, bed nucleus of the stria terminalis (BNST), perifornical area, anterior paraventricular nucleus, peduncular and tuberal lateral hypothalamus (TuLH), suprachiasmatic nucleus and medial amygdala. However, CTB/pro-TRH178-199 double-labeled cells were only found in the TuLH. The specificity of the retrograde tract-tracing result was confirmed by administering the anterograde tracer, Phaseolus vulgaris leuco-agglutinin (PHAL) into the TuLH. Double-labeled PHAL-pro-TRH boutons were identified in all subdivisions of the TMN. TMN neurons double-labeled for histidine decarboxylase ( Hdc )/PHAL, Hdc / Trh receptor ( Trhr ), and Hdc / Trh . Further confirmation of a TuLH-TRH neuronal projection to the TMN was established in a transgenic mouse that expresses Cre recombinase in TRH-producing cells following microinjection of a Cre recombinase-dependent AAV that expresses mCherry into the TuLH. We conclude that, in rodents, the TRH innervation of TMN originates in part from TRH neurons in the TuLH, and that this TRH population may contribute to regulate energy homeostasis through histamine Trhr- positive neurons of the TMN.},
	year = {2022},
	eissn = {1863-2661},
	pages = {2329-2347},
	orcid-numbers = {Sánchez-Jaramillo, Edith/0000-0002-5560-2645}
}

@article{MTMT:32886731,
	title = {Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation},
	url = {https://m2.mtmt.hu/api/publication/32886731},
	author = {Liu, Shengnan and Shen, Siyi and Yan, Ying and Sun, Chao and Lu, Zhiqiang and Feng, Hua and Ma, Yiruo and Tang, Zhili and Yu, Jing and Wu, Yuting and Gereben, Balázs and Mohácsik, Petra and Fekete, Csaba and Feng, Xiaoyun and Yuan, Feixiang and Guo, Feifan and Hu, Cheng and Shao, Mengle and Gao, Xin and Zhao, Lin and Li, Yuying and Jiang, Jingjing and Ying, Hao},
	doi = {10.1038/s41467-022-31154-1},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {13},
	unique-id = {32886731},
	issn = {2041-1723},
	year = {2022},
	eissn = {2041-1723},
	orcid-numbers = {Yuan, Feixiang/0000-0003-0232-2719; Guo, Feifan/0000-0001-6628-7647; Shao, Mengle/0000-0002-5488-9904; Jiang, Jingjing/0000-0003-1886-2613; Ying, Hao/0000-0002-8661-3670}
}

@article{MTMT:32583377,
	title = {Tanycyte specific ablation of diacylglycerol lipase alpha stimulates the hypothalamic‐pituitary‐thyroid axis by decreasing the endocannabinoid mediated inhibition of TRH release},
	url = {https://m2.mtmt.hu/api/publication/32583377},
	author = {Kővári, Dóra and Penksza, Veronika and Stiftné Szilvásy-Szabó, Anett and Sinkó, Richárd and Gereben, Balázs and Mackie, Ken and Fekete, Csaba},
	doi = {10.1111/jne.13079},
	journal-iso = {J NEUROENDOCRINOL},
	journal = {JOURNAL OF NEUROENDOCRINOLOGY},
	volume = {34},
	unique-id = {32583377},
	issn = {0953-8194},
	keywords = {tanycytes; HPT axis; Hypophysiotropic; TRH neurons; DAGLα},
	year = {2022},
	eissn = {1365-2826},
	orcid-numbers = {Kővári, Dóra/0000-0001-5346-822X}
}