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Hormone Action (hormone + action)
Kinds of Hormone Action Selected AbstractsThyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the HippocampusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2009M. A. Caria Years of effort have failed to establish a generally-accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse-perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine-induced responses of CA1 cells studied in vitro. [source] Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental FindingsJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2004R. T. Zoeller Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congential hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions. [source] Doublecortin as a marker of adult neuroplasticity in the canary song control nucleus HVCEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Jacques Balthazart Abstract It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn neurons. In the developing and adult mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic neurons and, as a part of the microtubule machinery, required for neuronal migration. We recently showed that in adult canaries, DCX-immunoreactive (ir) cells are present throughout the telencephalon, but the link between DCX and the active neurogenesis observed in songbirds remained uncertain. We demonstrate here that DCX labels recently born cells in the canary telencephalon and that, in parallel with changes in HVC volume, the number of DCX-ir cells is increased specifically in the HVC of testosterone-treated males compared with castrates, and in castrated testosterone-treated males paired with a female as compared with males paired with another male. The numbers of elongated DCX-ir cells (presumptive migrating neurons) and round multipolar DCX-ir cells (differentiating neurons) were also affected by the sex of the subjects and their photoperiodic condition (photosensitive vs photostimulated vs photorefractory). Thus, in canaries the endocrine state, as well as the social or photoperiodic condition independently of variation in steroid hormone action, affects the number of cells expressing a protein involved in neuronal migration specifically in brain areas that incorporate new neurons in the telencephalon. The DCX gene may be one of the targets by which testosterone and social stimuli induce seasonal changes in the volume of song nuclei. [source] The Effects of Steroid Hormones on the Transcription of Genes Encoding Enzymes of Oxidative PhosphorylationEXPERIMENTAL PHYSIOLOGY, Issue 1 2003Klaus Scheller Regulation of energy metabolism is one of the major functions of steroid hormones. In this process, mitochondria, by way of oxidative phosphorylation, play a central role. Depending on the energy needs of the cell, on the tissue, on the developmental stage and on the intensity of the hormonal stimulus, the response can be an activation of pre-existing respiratory chain components, an increased transcription of nuclear-encoded and/or mitochondrial-encoded respiratory chain enzyme (OXPHOS) genes and of biosynthesis of the respective enzyme subunits or, in extreme cases of high energy needs, an increase in the number of mitochondria and mitochondrial DNA content per cell. Some of the hormonally regulated systems involving effects on nuclear and mitochondrial OXPHOS genes are reviewed in this paper. The possible molecular mechanisms of steroid hormone action on nuclear and mitochondrial gene transcription and possible ways of coordination of transcription in these two separate cell compartments involving direct interaction of steroid receptors with hormone response elements in nuclear OXPHOS genes and in mitochondria and induction/activation of nuclear-encoded regulatory factors affecting mitochondrial gene transcription are presented. [source] Hormonal regulation of multiple promoters of the rat mitochondrial glycerol-3-phosphate dehydrogenase geneFEBS JOURNAL, Issue 14 2001Identification of a complex hormone-response element in the ubiquitous promoter B Rat mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is regulated by multiple promoters in a tissue-specific manner. Here, we demonstrate that thyroid hormone (3,5,3,-tri-iodo- l -thyronine) and steroid hormone but not the peroxisome proliferator clofibrate and retinoic acid stimulate the activation of the ubiquitous promoter B in a receptor-dependent manner, whereas the more tissue-restricted promoters A and C are not inducible by these hormones. Thyroid hormone action is mediated by a direct repeat +4 (DR+4) hormone-response element as identified by deletion and mutation analyses of promoter B in transient transfection analyses. The DR+4 element was able to bind to an in vitro translated thyroid hormone receptor in band-shift and supershift experiments. The hormone-response element comaps with a recognition site for the transcription factor Sp1, suggesting complex regulation of this sequence element. Mutation of this Sp1-recognition site reduces the basal promoter B activity dramatically in HepG2 and HEK293 cells in transient transfection and abolishes the binding of Sp1 in band-shift experiments. As demonstrated by Western-blot experiments, administration of tri-iodothyronine to euthyroid rats increases hepatic mGPDH protein concentrations in vivo. As it has recently been reported that human mGPDH promoter B is not regulated by tri-iodothyronine, this is the first example of a differentially tri-iodothyronine-regulated orthologous gene promoter in man and rat. [source] The cis -regulatory sequences required for expression of the Drosophila melanogaster adult cuticle gene ACP65AINSECT MOLECULAR BIOLOGY, Issue 4 2009M. Lestradet Abstract Post-embryonic development in insects requires successive molts. Molts are triggered by ecdysteroids, and the nature of the molt (larval, pupal or adult) is determined by juvenile hormones. The genes encoding cuticle proteins are targets of both classes of hormones, and therefore are interesting models to study hormone action at the molecular level. The Drosophila ACP65A cuticle gene is expressed exclusively during the synthesis of the adult exoskeleton, in epidermal domains synthesising flexible cuticle. We have examined the cis -regulatory sequences of ACP65A using phylogenetic comparisons and functional analysis, and find that only about 180 bp are essential, including an 81 bp intron. The restriction of ACP65A expression appears to depend on a strong repression mechanism. [source] The RNA coregulator SRA, its binding proteins and nuclear receptor signaling activityIUBMB LIFE, Issue 3 2008Shane M. Colley Abstract Nuclear receptor (NR) coregulators are key modulators of hormone signaling. Discovery of steroid receptor RNA activator (SRA), a coregulator that is active as a RNA, transformed thinking in the field of hormone action. The subsequent identification of SRA-binding coregulator proteins, including p68, SHARP and more recently SLIRP, has provided important insight into SRA's mechanism of action and potentially offers new opportunities to target NR signaling pathways for therapeutic gain. Here we outline advances in the field of NR coregulator biology, with a bias on recent progress in understanding SRA-protein interactions. © 2008 IUBMB IUBMB Life, 60(3): 159,164, 2008 [source] Novel Mechanisms for Feedback Regulation of Phospholipase C-, ActivityIUBMB LIFE, Issue 5 2002Irene Litosch Abstract The receptor-regulated phospholipase C- ,(PLC- ,) signaling pathway is an important component in a network of signaling cascades that regulate cell function. PLC- ,signaling has been implicated in the regulation of cardiovascular function and neuronal plasticity. The G q family of G proteins mediate receptor stimulation of PLC- ,activity at the plasma membrane. Mitogens stimulate the activity of a nuclear pool of PLC- ,. Stimulation of PLC- ,activity results in the rapid hydrolysis of phosphatidylinositol-4,5-bisphosphate, with production of inositol-1,4,5-trisphosphate and diacylglycerol, intracellular mediators that increase intracellular Ca 2+ levels and activate protein kinase C activity, respectively. Diacylglycerol kinase converts diacylglycerol to phosphatidic acid, a newly emerging intracellular mediator of hormone action that targets a number of signaling proteins. Activation of the G q linked PLC- ,signaling pathway can also generate additional signaling lipids, including phosphatidylinositol-3-phosphate and phosphatidylinositol-3,4,5-trisphosphate, which regulate the activity and/or localization of a number of proteins. Novel feedback mechanisms, directed at the level of G q and PLC- ,, have been identified. PLC- ,and regulators of G protein signaling (RGS) function as GTPase-activating proteins on G q to control the amplitude and duration of stimulation. Protein kinases phosphorylate and regulate the activation of specific PLC- ,isoforms. Phosphatidic acid regulates PLC- ,1 activity and stimulation of PLC- ,1 activity by G proteins. These feedback mechanisms coordinate receptor signaling and cell activation. Feedback mechanisms constitute possible targets for pharmacological intervention in the treatment of disease. [source] Hormonal regulation of temperature-induced growth in ArabidopsisTHE PLANT JOURNAL, Issue 4 2009Jon A. Stavang Summary Successful plant survival depends upon the proper integration of information from the environment with endogenous cues to regulate growth and development. We have investigated the interplay between ambient temperature and hormone action during the regulation of hypocotyl elongation, and we have found that gibberellins (GAs) and auxin are quickly and independently recruited by temperature to modulate growth rate, whereas activity of brassinosteroids (BRs) seems to be required later on. Impairment of GA biosynthesis blocked the increased elongation caused at higher temperatures, but hypocotyls of pentuple DELLA knockout mutants still reduced their response to higher temperatures when BR synthesis or auxin polar transport were blocked. The expression of several key genes involved in the biosynthesis of GAs and auxin was regulated by temperature, which indirectly resulted in coherent variations in the levels of accumulation of nuclear GFP,RGA (repressor of GA1) and in the activity of the DR5 reporter. DNA microarray and genetic analyses allowed the identification of the transcription factor PIF4 (phytochrome-interacting factor 4) as a major target in the promotion of growth at higher temperature. These results suggest that temperature regulates hypocotyl growth by individually impinging on several elements of a pre-existing network of signaling pathways involving auxin, BRs, GAs, and PIF4. [source] The intracrine hypothesis and intracellular peptide hormone actionBIOESSAYS, Issue 4 2003Richard N. Re There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. The intracellular/intracrine renin,angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well-established physiological system. The role of intracrine action in metazoan development is also considered. BioEssays 25:401,409, 2003. © 2003 Wiley Periodicals, Inc. [source] Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of lifeCLINICAL ENDOCRINOLOGY, Issue 4 2010Elisa Vaiani Summary Introduction, Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20,30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. Objective, To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Study design, Eighteen patients with PWS, aged 0·16,2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. Results, In 13 of 18 patients with PWS (72·2%), serum TT4 and/or FT4 levels were below the 2·5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. Conclusion, The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development. [source] Modulation of growth hormone action by sex steroidsCLINICAL ENDOCRINOLOGY, Issue 4 2006Udo J. Meinhardt Summary Growth hormone (GH) is a major regulator of growth, somatic development and body composition. Sex steroids can act centrally by regulating GH secretion and peripherally modulating GH responsiveness. This review addresses data of potential clinical relevance on how sex steroids modulate GH secretion and action, aiming to increase the understanding of sex steroid/GH interactions and leading to improved management of patients. Sex steroids regulate GH secretion directly as well as indirectly through IGF-I modulation. Testosterone stimulates GH secretion centrally, an effect dependent on prior aromatization to oestrogen. Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback inhibition. Whether oestrogen stimulates GH secretion centrally in females is unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and protein anabolism while exhibiting similar but independent actions of its own. Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of the liver. This is a concentration-dependent phenomenon that arises invariably from oral administration of therapeutic doses of oestrogen, an effect that can be avoided by using a parenteral route. This strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biological basis of sexual dimorphism in growth, development and body composition and practical information for the clinical endocrinologist. It calls for an appraisal of the diagnostic criteria for GH deficiency of GH stimulation tests, which currently are based on arbitrary cut-offs that do not take into account the shifting baseline from the changing gonadal steroid milieu. In the management of GH deficiency in the hypopituitary female, oestrogen should be administered by a nonoral route. In hypopituitary men, androgens should be replaced concurrently to maximize the benefits of GH. In the general population, the metabolic consequences of long-term treatment of women with oral oestrogen compounds, including selective oestrogen receptor modulators, are largely unknown and warrant study. [source] Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colonBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2000Mr D. C. Winter Background Oestrogens are important mitogens in epithelial cancers, particularly where tumours express complementary receptors. While the traditional model of oestrogen action involves gene-directed (genomic) protein synthesis, it has been established that more rapid, non-genomic steroid hormone actions exist. This study investigated the hypothesis that oestrogen rapidly alters cell membrane activity, intracellular pH and nuclear kinetics in a mitogenic fashion. Methods Crypts isolated from human distal colon and colorectal cancer cell lines were used as robust models. DNA replication and intracellular pH were measured by radiolabelled thymidine incorporation (12 h) and spectrofluorescence imaging respectively. Genomic protein synthesis, sodium,hydrogen exchanger (NHE) and protein kinase C (PKC) activity were inhibited with cycloheximide, ethylisopropylamiloride and chelerythrine chloride respectively. Results Oestrogen induced a rapid (less than 5 min) cellular alkalinization of crypts and cancer cells that was sensitive to NHE blockade (P < 0·01) or PKC inhibition (P < 0·01). Oestrogen increased thymidine incorporation by 44 per cent in crypts and by up to 38 per cent in cancer cells (P < 0·01), and this was similarly reduced by inhibiting the NHE (P < 0·01) or PKC (P < 0·05). Conclusion Oestrogen rapidly activates cell membrane and nuclear kinetics by a non-genomic mechanism mediated by PKC but not gene-directed protein synthesis. © 2000 British Journal of Surgery Society Ltd [source] Effects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Effect of inhibitors of mitogen-activated protein kinase kinase on ,1B -adrenoceptor phosphorylationAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1-2 2009R. Alcántara-Hernández Summary 1,Mitogen-activated protein kinases mediate hormone/neurotransmitter action on proliferation and differentiation and participate in receptor regulation. The effect of inhibitors of mitogen-activated kinase kinase (MEK) on ,1B -adrenoceptor phosphorylation state and function was studied using different cell lines. It was observed that at nanomolar concentrations the MEK inhibitors, PD98059 (2,-amino-3,-methoxyflavone) and UO126 [1,4-(diamino-2,3-dicyano/1,4-bis-(2-aminophenylthio)-butadiene], increased ,1B -adrenoceptor phosphorylation and diminished the functional response of this receptor to noradrenaline. These agents did not alter the action of lysophosphatidic acid. 2,Staurosporine (IC50 , 0.8 nm) (a general protein kinase inhibitor) and bis-indolyl-maleimide I (IC50 , 200 nm) (a selective protein kinase C inhibitor) inhibited PD98059-induced ,1B -adrenoceptor phosphorylation. In contrast, neither wortmannin (phosphoinositide 3-kinase inhibitor) nor genistein (protein tyrosine kinase inhibitor) had any effect. The data suggest the possibility that MEK might exert control on the activity of the enzymes that regulate receptor phosphorylation, such as G-protein-coupled receptor kinases, protein kinase C or serine/threonine protein phosphatases. 3,Coimmunoprecipitation studies showed a constant association of total extracellular signal-regulated kinase 2 (ERK2) with ,1B -adrenoceptors. Association of phospho-ERK 1/2 to ,1B -adrenoceptors increased not only in response to agonist but also in response to agents that increase ,1B -adrenoceptor and ERK1/2 phosphorylation [such as endothelin-1, phorbol 12-myristate-13-acetate (PMA) and epidermal growth factor (EGF)]; not surprisingly, PD98059 decreased this effect. 4,Our data show that blockade of MEK activity results in increased ,1B -adrenoceptor phosphorylation, diminished adrenoceptor function and perturbation of receptor,ERK1/2 interaction. [source] | |||||||||||||