Central regulatory mechanisms involved in the development of the "low T3 syndrome  Page description

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Details of project

  
Identifier
46492
Type K
Principal investigator Fekete, Csaba
Title in Hungarian Az "alacsony T3 szindróma" kialakulásáért felelős központi idegrendszeri szabályozó mechanizmusok tanulmányozása patkányban
Title in English Central regulatory mechanisms involved in the development of the "low T3 syndrome
Panel Neurosciences
Department or equivalent Lendület Laboratory of Integrative Neuroendocrinology (Institute of Experimental Medicine)
Participants Liposits, Zsolt
Wittmann, Gábor
Starting date 2004-01-01
Closing date 2007-12-31
Funding (in million HUF) 8.050
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
A pályázat fő célja az éhezés és fertőzés hatására kialakuló centrális hipotiroidizmus kialakulásáért felelős központi idegrendszeri szabályozó mechanizmusok tanulmányozása volt. Kimutattuk, hogy a leptin, inzulin és glükóz eltérő hatást fejt ki az arcuatus idegmag sejtjeire és csak a leptin képes kivédeni az éhezés hatására kialakuló centrális hipotiroidizmust. Leírtuk, hogy az AGRP TRH idegsejtekre kifejtett gátló hatását elsősorban a 4-es típusú melanokortin receptor (MC4-R) közvetíti. Igazoltuk, hogy a PVN MC4-R tartalmú idegsejtjein a legtöbb AGRP tartalmú terminális közelében nem figyelhetők meg α-MSH-tartalmú végződések, valószínűsítve, hogy az AGRP a PVN-ben inverz agonistaként hathat. Leírtuk, hogy LPS kezelés a pajzsmirigyhormonok szintjének változásától függetlenül D2 aktivitás fokozódást eredményez a mediobazális hipotalamuszban a tanycytákban. Továbbá azonosítottuk a D2 promoter NF-kB kötőhelyét. Ezek alapján feltételezzük, hogy LPS hatására a megemelkedett D2 aktivitás az eredményezett lokális hipertiroidizmus révén hozzájárul a TRH idegsejtek gátlásához.
Results in English
The long term goal of the proposed studies was the examination of the hypothalamic regulatory systems involved in the development of the central hypothyroidism induced by fasting or infection. We have described that leptin, insulin and glucose have different effects on the neurons of the arcuate nucleus. In addition, only leptin is able to reverse the fasting induced changes of the hypothalamic-pituitary-thyroid axis. We have demonstrated that the effect of AGRP on the hypophysiotropic TRH neurons is primarily mediated by the melanocortin 4 receptor (MC4-R). In addition, we have provided evidence that α-MSH-containing varicosities are not present in the proximity of the AGRP terminals on the surface of the MC4-R-producing cells in the PVN, suggesting that AGRP acts as an inverse agonist in the PVN. We have demonstrated that LPS induces an increase of D2 activity in the tanycytes of the mediobasal hypothalamus. These changes are independent from the changes of the peripheral thyroid hormone level. Furthermore, we have identified the NF-kB binding cite of the D2 promoter. Based on these data, we hypothesize that the LPS induced increase of D2 activity results in a local hyperthyroidism in the PVN that contribute to the LPS induced inhibition of the hypophysiotropic TRH neurons.
Full text http://real.mtak.hu/1456/
Decision
Yes





 

List of publications

  
Fekete C, Sarkar S, Lechan RM: Relative contribution of brainstem afferents to the cocaine- and amphetamine-regulated transcript (CART) innervation of thyrotropin-releasing hormone synthesizing neurons, Brain Research, 2005
Wittmann G, Lechan RM, Liposits Z, Fekete C: Glutamatergic innervation of corticotropin-releasing hormone- and thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus of the ra, Brain Research, 2005
Wittmann G, Liposits Z, Lechan RM, Fekete C: Origin of cocaine- and amphetamine-regulated transcript-containing axons innervating hypophysiotropic corticotropin-releasing hormone-synthesizing neurons in the rat, Endocrinology, 2005
Singru PS, Fekete C, Lechan RM: Neuroanatomical evidence for participation of the hypothalamic dorsomedial nucleus (DMN) in regulation of the hypothalamic paraventricular nucleus (PVN) by alpha-melanocy, Brain Research, 2005
Menyhert J, Wittmann G, Hrabovszky E, Keller E, Liposits Z, Fekete C.: Interconnection between orexigenic neuropeptide Y- and anorexigenic alpha-melanocyte stimulating hormone-synthesizing neuronal systems of the human hypothalamus, Brain Research, 2006
Hrabovszky E, Kallo I, Turi GF, May K, Wittmann G, Fekete C, Liposits Z.: Expression of vesicular glutamate transporter-2 in gonadotrope and thyrotrope cells of the rat pitmulating hormone-synthesizing neuronal systems of the human hypothalamus, Endocrinology, 2006
Zeold A, Doleschall M, Haffner MC, Capelo LP, Menyhert J, Liposits Z, da Silva WS, Bianco AC, Kacskovics I, Fekete C, Gereben B.: Characterization of the nuclear factor-kappa B responsiveness of the human dio2 genepitmulating hormone-synthesizing neuronal systems of the human hypothalamus, Endocrinology, 2006
Fekete C, Lechan RM.: Neuroendocrine implications for the association between cocaine- and amphetamine regulated transcript (CART) rmone-synthesizing neuronal systems of the human hypothalamus, Peptides, 2006
Menyhert J, Wittmann G, Hrabovszky E, Szlavik N, Keller E, Tschop M, Liposits Z, Fekete C: Distribution of ghrelin-immunoreactive neuronal networks in the human hypothalamus., Brain Research, 2006
WITTMANN G, MARKS D, LIPOSITS Z, CONE R, LECHAN RM, FEKETE C: Morphological evidence suggesting a role of agouti-related protein as an inverse agonist at melanocortin 4 receptors in the hypothalamic PVN, SFN, 2006
Fekete C, Marks DL, Sarkar S, Emerson CH, Rand WM, Cone RD, Lechan RM: Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse., Endocrinology, 2004
Fekete C, Sarkar S, Christoffolete MA, Emerson CH, Bianco AC, Lechan RM: Bacterial lipopolysaccharide (LPS)-induced type 2 iodothyronine deiodinase (D2) activation in the mediobasal hypothalamus (MBH) is independent of the LPS-induced fall ..., Brain Research, 2005
Fekete C, Singru PS, Sarkar S, Rand WM, Lechan RM: Ascending Brainstem Pathways are Not Involved in Lipopolysaccharide-Induced Suppression of TRH Gene Expression in the Hypothalamic Paraventricular Nucleus., Endocrinology, 2005
Hrabovszky E, Wittmann G, Turi GF, Liposits Z, Fekete C: Hypophysiotropic thyrotropin-releasing hormone and corticotropin-releasing hormone neurons of the rat contain vesicular glutamate transporter-2, Endocrinology, 2005
Fekete C, Singru PS, Sanchez E, Sarkar S, Christoffolete MA, Riberio RS, Rand WM, Emerson CH, Bianco AC, Lechan RM: Differential Effects of Central Leptin, Insulin or Glucose Administration During Fasting on the Hypothalamic-Pituitary-Thyroid (HPT) Axis and Feeding-Related Neurons ...., Endocrinology, 2006
Fekete C, Freitas BC, Zeold A, Wittmann G, Kadar A, Liposits Z, Christoffolete MA, Singru P, Lechan RM, Bianco AC, Gereben B: Expression patterns of Wsb-1 and Usp-33 underlie cell-specific post-translational control of type 2 deiodinase (d2) in the rat brain, Endocrinology, 2007
Fekete C, Lechan RM: Negative feedback regulation of hypophysiotropic thyrotropin-releasing hormone (TRH) synthesizing neurons: Role of neuronal afferents and type 2 deiodinase, Frontiers in Neuroendocrinology, 2007
Fuzesi T, Wittmann G, Liposits Z, Lechan RM, Fekete C: Contribution of noradrenergic and adrenergic cell groups of the brainstem and agouti-related protein (AGRP)-synthesizing neurons of the arcuate nucleus to neuropeptide-Y innervation of corticotropin-releasing hormone neurons in hypothalamic paraventricular nucleus of the rat, Endocrinology, 2007
Menyhért J, Wittmann G, Lechan RM, Keller É, Liposits Z, Fekete C: Cocaine- and amphetamine regulated transcript (CART) is colocalized with the orexigenic NPY and AGRP and absent from the anorexigenic [alpha]-MSH neurons in the infundibular nucleus of the human hypothalamus, Endocrinology, 2007
Wittmann G, Deli L, Kallo I, Hrabovszky E, Watanabe M, Liposits Z, Fekete C: Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus, Journal of Comparative Neurology, 2007




 

Events of the project

  
2011-04-05 15:40:46
Kutatóhely váltás
A kutatás helye megváltozott. Korábbi kutatóhely: Endokrin Neurobiológia Kutatócsoport (MTA Kísérleti Orvostudományi Kutatóintézet), Új kutatóhely: Integratív Neuroendokrinológiai Kutatócsoport (MTA Kísérleti Orvostudományi Kutatóintézet).



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