17 research outputs found
A hipotalamikus neuronális energiaszint szabályozásának vizsgálata: Az NTPDázok, mint lehetsĂ©ges energia-regulátorok szerepe a pozitĂv gonadotropin feedback során. = Regulation of neuronal energy levels in the hypothalamus: NTPDases as possible energy regulators of the positive gonadotrophin feedback.
Pályázatunk fĹ‘ cĂ©lja, hogy a serkentĹ‘ idegi működĂ©shez szĂĽksĂ©ges celluláris energiaszint „korlátozó”, vagy Ă©ppen „megengedő” szerepĂ©t vizsgáljuk. A hypothalamicus (HT) NTPDáz3 ATP-szabályzĂł szerepĂ©t a tervezettnĂ©l szĂ©lesebb spektrumban vizsgáltuk, valamint figyelembe vettĂĽk, hogy a HT egyszerre több homeosztatikus funkciĂł idegi központja. EzĂ©rt figyelembe vettĂĽk az Ă©rintett homeosztatikus folyamatokat szabályzĂł idegi struktĂşrák átfedĂ©seit Ă©s a közös mechanizmusokat. A kĂsĂ©rletek kĂ©t, egymással szorosan összefĂĽggĹ‘ folyamat elemzĂ©sĂ©re terjedtek ki, melyek eredmĂ©nyei a következĹ‘k szerint foglalhatĂłk össze: 1. A mitokondriális metabolizmus, beleĂ©rtve az NTPDáz3 aktivitását is, valamint a hypothalamus O2 ellátása, az ösztrusz ciklushoz, illetve annak egyes fázisaihoz igazodĂł hullámzĂł tendenciát mutatott; Ez a hullámzĂł tendencia az állatok több mint 80 %-ában a hypothalamusnak csak az egyik fĂ©ltekĂ©jĂ©ben mutatkozott, mĂg az ellenoldali fĂ©lteke mitokondriális metabolizmusa a ciklus minden fázisában egyenletes, kiegyenlĂtett tendenciát mutatott. 2. Az ADP-fĂĽggĹ‘ 3-as tĂpusĂş mitokondriális lĂ©gzĂ©s korrelál a korábbi kĂsĂ©rleteink szerint leĂrt gyors ĂĽtemű, nagyszámĂş hypothalamicus excitatĂłrikus szinapszis lĂ©trejöttĂ©nek Ă©s aktivitásának idejĂ©vel, ami az ösztrusz ciklus proösztrusz-korai ösztrusz fázisainak idejĂ©re esik. 3. Az 1-5-ös tĂpusĂş mitokondriális lĂ©gzĂ©s elemzĂ©se azt valĂłszĂnűsĂti, hogy a mitokondriális NTPDáz3 blokkolása átfogĂłan lassĂtja a mitokondrium metabolizmusát. | The project’s main goal was to examine the limiting/permissive role of the cellular energy levels in hypothalamic (HT) excitatory neuronal activity. Considering that the HT is the regulatory center of more than one homeostatic systems, investigations on the ATP-regulating activity of hypothalamic NTPDase3 were more detailed than originally outlined. Hypothalamic structural and functional overlaps were considered. Studies included two major lines of experiments with result summarized as follows: 1.) The mitochondrial metabolism, including the NTPDase3 activity, and the hypothalamic O2 supply showed a fluctuating pattern corresponding to the phases of the estrous cycle. This phenomenon could only be observed in either the left or right hypothalamic hemispheres in cca. 80 percent of the animals, while the contralateral hemishere showed no such fluctuations. 2.) The ADP-dependent State 3 (St3) mitochondrial respiration correlates with the rapid generation and function of excitatory synapses during late proestrus and early estrus. 3.) Analysis of St1-5 data imply that inhibition of mitochondrial NTPDase3 function leads to overall down-regulation of mitochondrial metabolism
Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin
Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose
tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five bestknown peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake
Comparative analysis and functional implications of ligand dependent changes in estrogen- and thyroid hormone receptor expression in the developing cerebellum
Abstract
Trophic hormones are important regulators of CNS development and function. In particular,
estrogen (E2) and thyroid hormones (THs) regulate cell migration, differentiation,
proliferation and synaptogenesis/network formation during cerebellar development. These
hormone-regulated events involve the binding of hormone ligands to their cognate receptors
that function as transcription factors to activate relevant genes for the adequate orchestration
of developmental processes. Recent reports implicate a complex mechanism through which
E2 and THs influence the expression levels of each other’s receptors (ERs and TRs) to
precisely mediate developmental signals. Here we examined the effects of the presence or
absence of E2 and THs on the expression levels of their receptor mRNAs and proteins.
Cerebellar granule cell cultures were treated with either E2, T3, T4 or a combination of these
hormones, and resulting receptor expression levels were determined by quantitative PCR and
Western blot techniques. Results were compared to non-treated controls and to samples
obtained from 14-day-old in situ cerebella. Additionally, we determined the effects that glial
cells might have on the regulation of ER-TR expression levels. Results show that: (i) ER and
TR expression levels depend on the individual or combined presence/absence of E2 and THs;
(ii) glial cells are important mediators in the hormonal regulation of neuronal ER-TR
expression, and (iii) loss of tissue integrity results in characteristic changes in ER-TR
expression levels. These observations suggest that both E2 and THs are required for the
precise orchestration of cerebellar development and that alterations in the tissue concentration
of either of the hormones may influence signaling mechanisms that are driven by both E2 and
THs. Comparison of data from in vitro and in situ samples also revealed a shift in receptor
expression levels after loss of tissue integrity, likely indicating possible adjusting/regenerative
mechanisms after cerebellar tissue injury
Possible hypothalamic laterality in the central regulation of GnRH release: thoughts that might lead to a novel approach in hypothalamic studies
The midcycle E2 surge induces a synaptic reorganization
in the mediobasal hypothalamus (MBH), thus increasing
the ratio of stimulatory/inhibitory synapses. This synaptic
reorganization disinhibits GnRH neurons and leads to an LH
surge. Synaptic functions are energy dependent and require
mitochondrial ATP production. Ectonucleoside triphosphate
diphosphohydrolase 3 (NTPDase3) may play a crucial role
in the regulation of mitochondrial ATP levels in stimulatory
MBH neurons. The positive gonadophin feedback involves
the generation and function of large numbers of hypothalamic
stimulatory synapses, thus, it might be associated with increased
mitochondrial ATP production and increased mitochondrial
respiration (mr). Anatomically, there are paired brain areas
in the two hemispheres and unpaired structures along the
anatomical midline. Distinct sides of paired brain areas
usually regulate distinct physiological processes, rather than
sharing roles to regulate the exact same functions. However,
there are certain brain regions with no known functional
differences between the two sides. One such brain area is the
MBH, which has always been investigated as an unpaired
midline structure despite its clearly symmetric anatomical
characteristics. Investigation of mr in MBH synaptosomal
fractions in our laboratory has indicated that besides ipsylateral
intrahypothalamic differences (i.e., differences between the
lateral and medial regions of the MBH on the same side) a
functional laterality may exist between homologous areas
of symmetric hypothalamic structures. Therefore, we have
investigated mr rates, with special regard to ADP-dependent
state 3 mr, in the MBH with isolated left and right sides. Our
initial results imply that the MBH regulation of the E2-induced
gonadotrophin surge is unilateral, and that there is an urging
need for a technical solution to identify in vivo the dominant
hypothalamic side that enters into the positive gonadotrophin
phase of the estrous cycle
Interactive hormonal regulation of cerebellar estrogen- and thyroid hormone receptor expression in primary cerebellar granule cell culture
Ösztrogén- és pajzsmirigyhormon receptorok expressziójának ligandum-függő változásai a fejlődő kisagyban
A kisagy fejlĹ‘dĂ©sĂ©ben meghatározĂł szerepet játszanak az Ăşgynevezett trĂłfikus hormonok. Ezek közĂĽl is kiemelkednek az ösztrogĂ©nek Ă©s a pajzsmirigy hormonjai, melyek specifikus receptorok aktiválása Ăştján szabályzĂł szerepet játszanak a sejtmigráciĂł, differenciálĂłdás, sejtproliferáciĂł, valamint a kisagyi összeköttetĂ©s-rendszer kiĂ©pĂtĂ©sĂ©ben. Az utĂłbbi Ă©vek irodalmi adatai arra engednek következtetni, hogy az emlĂtett kĂ©t hormoncsalád tagjai kölcsönösen befolyást gyakorolnak egymás receptorainak a kifejezĹ‘dĂ©si szintjeire. A feltĂ©telezĂ©sek szerint egy esetleges, az ösztrogĂ©n- Ă©s pajzsmirigyhormon receptorok között lĂ©tezĹ‘ interaktĂv mechanizmus komplexebb mĂłdon, de precĂzebben szabályozhatja a korai posztnatális szövet-fejlĹ‘dĂ©stani esemĂ©nyeket a kisagyban, ezĂ©rt a kĂ©rdĂ©s behatĂł vizsgálata Ă©lettani Ă©s klinikai szempontbĂłl is indokolt.
Jelen vizsgálatunkban arra a kĂ©rdĂ©sre kerestĂĽnk választ, hogy ösztrogĂ©n Ă©s az egyes pajzsmirigyhormonok (fiziolĂłgiás koncentráciĂłban valĂł) jelenlĂ©te vagy hiánya hogyan befolyásolja az adott hormon specifikus receptorának a kifejezĹ‘dĂ©si szintjĂ©t primer kisagyi sejttenyĂ©szetben. HĂ©t napos patkányok kisagyábĂłl kĂ©szĂĽlt olyan primer sejttenyĂ©szeteket hoztunk lĂ©tre, melyek vagy tartalmaztak termĂ©szetes mĂłdon szaporodĂł glia sejteket is, vagy pedig a glia fejlĹ‘dĂ©sĂ©t kĂsĂ©rletesen blokkoltuk. Ilyen körĂĽlmĂ©nyek között, a kĂsĂ©rletesen manipulált hormonális környezetben nem csupán a kĂĽlönállĂł- Ă©s kombinált hormonhatásokat,
de a glia jelenlĂ©tĂ©nek vagy hiányának a következmĂ©nyeit is megfigyelhettĂĽk. EredmĂ©nyeinket minden esetben összehasonlĂtottuk hasonlĂł korĂş (fejlettsĂ©gi szintű) in situ kisagybĂłl vett minták mĂ©rĂ©si eredmĂ©nyeivel. Annak Ă©rdekĂ©ben, hogy átfogĂłbb kĂ©pet kapjunk az ösztrogĂ©nĂ©s
pajzsmirigyhormonok receptorainak kifejezĹ‘dĂ©si viszonyairĂłl, Western blot technikával határoztuk meg a receptor fehĂ©rjĂ©k relatĂv mennyisĂ©gĂ©t, Ă©s kvalitatĂv PCR technika alkalmazásával határoztuk meg a vonatkozĂł receptorok mRNS szintjeit. EredmĂ©nyeink egyĂ©rtelműen mutatják, hogy mind az ösztrogĂ©n receptorok, mind pedig a
pajzsmirigyhormon receptorok kifejezıdĂ©si szintje fĂĽgg mindkĂ©t hormon jelenlĂ©tĂ©tĹ‘l, Ă©s azt is kimutattuk, hogy a glia sejtek is fontos szabályozĂł szerepet töltenek be az egyes vizsgált hormon receptorok expressziĂłjának a szabályozásában. Ugyanakkor az in situ kisagyi mintákkal törtĂ©nt összehasonlĂtĂł vizsgálatok azt is megmutatták, hogy a szöveti integritás elveszĂtĂ©se is egyĂ©rtelmű hatással van a vizsgált receptorok mennyisĂ©gi viszonyaira, egyĂşttal
felhĂvva a figyelmet az in vitro Ă©s in vivo kĂsĂ©rleti eredmĂ©nyek közötti relevancia-kĂ©rdĂ©sekre is.
EredmĂ©nyeink határozottan mutatják, hogy a kisagy megfelelĹ‘ fejlĹ‘dĂ©sĂ©ben meghatározĂł szerepe van az ösztrogĂ©n Ă©s pajzsmirigyhormonok fiziolĂłgiás arányának, Ă©s arra is adatokat szolgáltatunk, hogy a szöveti integritás elveszĂtĂ©se (szövetsĂ©rĂĽlĂ©s) kompenzáciĂłs változásokat
idéz élő a fejlődő kisagy nukleáris receptorainak expressziójában
Analysis of ligand-dependent changes in estrogen receptor and thyroid hormone receptor mRNA and protein expression in the developing rat cerebellum
Ligand-induced changes in Oestrogen and thyroid hormone receptor expression in the developing rat cerebellum : A comparative quantitative PCR and Western blot study
Abstract
Oestrogen (E2) and thyroid hormones (THs) are key regulators of cerebellar development. Recent reports implicate a complex mechanism through which E2 and THs influence the expression levels of each other's receptors (ERs and TRs) to precisely mediate developmental signals and modulate signal strength. We examined the modulating effects of E2 and THs on the expression levels of their receptor mRNAs and proteins in cultured cerebellar cells obtained from 7-day-old rat pups. Cerebellar granule cell cultures were treated with either E2, THs or a combination of these hormones, and resulting receptor expression levels were determined by quantitative PCR and Western blot techniques. The results were compared to non-treated controls and to samples obtained from 14-day-old in situ cerebella. Additionally, we determined the glial effects on the regulation of ER-TR expression levels. The results show that (i) ER and TR expression depends on the combined presence of E2 and THs; (ii) glial cells mediate the hormonal regulation of neuronal ER-TR expression and (iii) loss of tissue integrity results in characteristic changes in ER-TR expression levels. These observations suggest that both E2 and THs, in adequate amounts, are required for the precise orchestration of cerebellar development and that alterations in the ratio of E2/THs may influence signalling mechanisms involved in neurodevelopment. Comparison of data from in vitro and in situ samples revealed a shift in receptor expression levels after loss of tissue integrity, suggesting that such adjusting/regenerative mechanisms may function after cerebellar tissue injury as well
Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture
Thyroid hormones (THs) and oestrogens are crucial in the regulation of cerebellar development. TH receptors (TRs) mediate these hormone effects and are regulated by both hormone families. We reported earlier that THs and oestradiol (E2) determine TR levels in cerebellar cell culture. Here we demonstrate the effects of low concentrations (10–10 M) of the endocrine disruptor (ED) bisphenol A (BPA) on the hormonal (THs, E2) regulation of TRα,β in rat cerebellar cell culture. Primary cerebellar cell cultures, glia-containing and glia-destroyed, were treated with BPA or a combination of BPA and E2 and/or THs. Oestrogen receptor and TH receptor mRNA and protein levels were determined by real-time qPCR and Western blot techniques. The results show that BPA alone decreases, while BPA in combination with THs and/or E2 increases TR mRNA expression. In contrast, BPA alone increased receptor protein expressions, but did not further increase them in combination with THs and/or E2. The modulatory effects of BPA were mediated by the glia; however, the degree of changes also depended on the specific hormone ligand used. The results signify the importance of the regulatory mechanisms interposed between transcription and translation and raise the possibility that BPA could act to influence nuclear hormone receptor levels independently of ligand–receptor interaction