Nongenomic Actions (nongenomic + action)

Distribution by Scientific Domains

Selected Abstracts

Nongenomic Actions of Adrenal Steroids in the Central Nervous System

N. K. Evanson
Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, although a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. We review the nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability to treat human disease as well as reduce the side-effects of the steroid treatments already in use. [source]

Presence of membrane ecdysone receptor in the anterior silk gland of the silkworm Bombyx mori

FEBS JOURNAL, Issue 15 2004
Mohamed Elmogy
Nongenomic action of an insect steroid hormone, 20-hydroxyecdysone (20E), has been implicated in several 20E-dependent events including the programmed cell death of Bombyx anterior silk glands (ASGs), but no information is available for the mode of the action. We provide evidence for a putative membrane receptor located in the plasma membrane of the ASGs. Membrane fractions prepared from the ASGs exhibit high binding activity to [3H]ponasterone A (PonA). The membrane fractions did not contain conventional ecdysone receptor as revealed by Western blot analysis using antibody raised against Bombyx ecdysone receptor A (EcR-A). The binding activity was not solubilized with 1,m NaCl or 0.05% (w/v) MEGA-8, indicating that the binding sites were localized in the membrane. Differential solubilization and temperature-induced phase separation in Triton X-114 showed that the binding sites might be integrated membrane proteins. These results indicated that the binding sites are located in plasma membrane proteins, which we putatively referred to as membrane ecdysone receptor (mEcR). The mEcR exhibited saturable binding for [3H]PonA (Kd = 17.3 nm, Bmax = 0.82 pmol·mg,1 protein). Association and dissociation kinetics revealed that [3H]PonA associated with and dissociated from mEcR within minutes. The combined results support the existence of a plasmalemmal ecdysteroid receptor, which may act in concert with the conventional EcR in various 20E-dependent developmental events. [source]

Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis

H.-C. Tillmann
Abstract Background, Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge. Methods, Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry. Results, Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone). Conclusion, This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect. [source]

GPR30 Differentially Regulates Short Latency Responses of Luteinising Hormone and Prolactin Secretion to Oestradiol

D. Lebesgue
Rapid, nongenomic actions of 17,-oestradiol (E2) on hypothalamic neurones that may be relevant to reproductive function were described decades ago. The orphan G protein-coupled receptor, GPR30, was recently shown to bind oestrogens and to trigger rapid signalling in vitro, and is expressed in several rat and human brain regions, including the hypothalamus. We used two complementary approaches to investigate the role of GPR30 in hypothalamic responses to E2 that are relevant to reproductive physiology. Serial blood sampling after the acute administration of the selective GPR30 agonist G1 was used to assess the role of GPR30 in short latency negative-feedback inhibition of luteinising hormone (LH) secretion and facilitation of prolactin secretion in ovariohysterectomised female rats. In vivo RNA interference (RNAi), mediated by adeno-associated virus-expressing small hairpin RNA (shRNA) infused into the mediobasal hypothalamus, was used to study the effects of GPR30 knockdown on these rapid responses to E2. Longer-term actions of E2 on female sexual behaviour (lordosis) were also examined in female rats subjected to in vivo RNAi. Administration of E2 or G1 triggered a short latency surge of prolactin secretion, and animals subjected to GPR30 RNAi showed significantly less E2 -dependent prolactin release than animals receiving control virus. G1 did not mimic E2 negative-feedback inhibition of LH secretion, and GPR30 RNAi did not interfere with E2 suppression of LH or facilitation of lordosis behaviour. These findings suggest that activation of GPR30 promotes short latency prolactin secretion but does not mediate E2 negative-feedback inhibition of LH secretion or E2 facilitation of female reproductive behaviour. [source]

Thyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the Hippocampus

M. 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]

Expanding view of aldosterone action, with an emphasis on rapid action

Gavin P. Vinson
Summary 1. The actions of aldosterone beyond the ,mineralocorticoid' designation continue to attract intense interest. In recent years, two aspects have received particular attention. These are, first, the potentially damaging direct actions of aldosterone on the heart and vascular system, and the clear benefit, as illustrated by the Randomized Aldactone Evaluation Study and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival trials, of including antialdosterone therapy in the treatment of cardiovascular disease. 2. Second, the importance of non-genomic actions of aldosterone has become clear, some of which might possibly be mediated by distinct membrane receptors. Over the past 5 years, evidence has arisen to bring these two aspects together, and now emphasizes the role of rapid, nongenomic actions of aldosterone on cardiovascular events. 3. However, despite many years of study, there is still no clear view of the nature of the receptors mediating non-genomic responses. We examine the evidence, and suggest that in many cases non-genomic actions are attributable to classical mineralocorticoid receptors. [source]