Transcriptional and metabolic effects of glucocorticoid receptor α and β signaling in zebrafish.


:In humans and zebrafish, 2 glucocorticoid (GC) receptor (GR) splice variants exist: the canonical GR α-isoform (GRα), and the GRβ. In the present study, we have used the zebrafish model system in order to reveal genes affected by each of these 2 receptor isoforms. By injecting zebrafish embryos with different splice-blocking morpholinos, we could knock down both GR isoforms or could target the alternative splicing of the GR pre-mRNA in favor of the GRβ. In addition, specific GRβ overexpression was achieved by injecting mRNA. Embryos were treated with the synthetic GC dexamethasone, and transcriptome analysis was performed. Two distinct gene clusters were found that were regulated by GRα: one that was regulated by GRα under basal conditions (presence of endogenous cortisol only), and one that was regulated upon increased activation of GRα (using a pharmacological dose of dexamathasone). GRβ may act as a dominant-negative inhibitor of GRα when GRβ is overexpressed and the GRα expression level is knocked down simultaneously. However, without GRα knockdown, no evidence for this activity was found. In addition, the data indicate regulation of gene transcription through other mechanisms of action by GRβ. We also investigated the concentrations of several metabolites using nuclear magnetic resonance spectroscopy. We found that dexamethasone treatment and knockdown of GRα together with overexpression of GRβ had opposite effects on glucose, amino acid, and fatty acid levels. Thus, we have shed new light on the molecular mechanisms of GC-induced effects on metabolism, which are known to increase the risk of obesity, hyperglycemia, and diabetes.






Chatzopoulou A,Roy U,Meijer AH,Alia A,Spaink HP,Schaaf MJ




Has Abstract


2015-05-01 00:00:00












  • Insulin and insulin-like growth factor I binding to cultured rat glomerular mesangial cells.

    abstract::The potential effects of insulin and insulin-like growth factor I (IGF-I) on mesangial cell (MC) metabolism and growth were examined. Radiolabeled insulin or IGF-I were incubated with cell membranes from rapidly proliferating (subconfluent) or nonproliferating (confluent) MC in the presence of increasing concentration...


    pub_type: 杂志文章


    authors: Abrass CK,Raugi GJ,Gabourel LS,Lovett DH

    更新日期:1988-11-01 00:00:00

  • Changes in retinoic acid receptor messenger ribonucleic acid levels in the vitamin A-deficient rat testis after administration of retinoids.

    abstract::Recently, we have reported that retinoic acid (RA), similarly to retinol acetate, is able to reinitiate spermatogenesis in vitamin A-deficient rats. Here, we investigated the expression of RA receptors RAR alpha, RAR beta, RAR gamma, and retinoid X receptor RXR alpha by Northern blot analysis of poly(A)+ RNA of testes...


    pub_type: 杂志文章


    authors: van Pelt AM,van den Brink CE,de Rooij DG,van der Saag PT

    更新日期:1992-07-01 00:00:00

  • In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.

    abstract::Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte ...


    pub_type: 杂志文章


    authors: Linscheid P,Seboek D,Nylen ES,Langer I,Schlatter M,Becker KL,Keller U,Müller B

    更新日期:2003-12-01 00:00:00

  • Thyronamines are isozyme-specific substrates of deiodinases.

    abstract::3-Iodothyronamine (3-T 1 AM) and thyronamine (T AM) are novel endogenous signaling molecules that exhibit great structural similarity to thyroid hormones but apparently antagonize classical thyroid hormone (T(3)) actions. Their proposed biosynthesis from thyroid hormones would require decarboxylation and more or less ...


    pub_type: 杂志文章


    authors: Piehl S,Heberer T,Balizs G,Scanlan TS,Smits R,Koksch B,Köhrle J

    更新日期:2008-06-01 00:00:00

  • Insulin/insulin-like growth factor-I hybrid receptors with high affinity for insulin are developmentally regulated during neurogenesis.

    abstract::The extensive colocalization of insulin receptor (IR) and insulin-like growth factor-I receptor (IGFR) messenger RNAs during central nervous system development, together with the effects of insulin and IGF-I in neurogenesis, raises the question of how stage- and factor-specific signaling occurs. Thus, it is necessary ...


    pub_type: 杂志文章


    authors: García-de Lacoba M,Alarcón C,de la Rosa EJ,de Pablo F

    更新日期:1999-01-01 00:00:00

  • Angiotensin II-induced mitogen-activated protein kinase phosphatase-1 expression in bovine adrenal glomerulosa cells: implications in mineralocorticoid biosynthesis.

    abstract::Angiotensin II (AngII) stimulates aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. AngII also triggers the MAPK pathways (ERK1/2 and p38). Because ERK1/2 phosphorylation is a transient process, phosphatases could play a crucial role in the acute steroidogenic response. Here we show that the dual...


    pub_type: 杂志文章


    authors: Casal AJ,Ryser S,Capponi AM,Wang-Buholzer CF

    更新日期:2007-11-01 00:00:00

  • Maternal growth hormone treatment increases placental diffusion capacity but not fetal or placental growth in sheep.

    abstract::We tested the hypothesis that chronic maternal GH administration would increase fetal substrate supply, increase maternal and fetal insulin-like growth factor I (IGF-I) concentrations, and therefore enhance growth in the late gestation fetal sheep. Eleven ewes received bovine GH 0.1 mg/kg twice daily for 10 days, wher...


    pub_type: 杂志文章


    authors: Harding JE,Evans PC,Gluckman PD

    更新日期:1997-12-01 00:00:00

  • Novel Hypothalamic Mechanisms in the Pathophysiological Control of Body Weight and Metabolism.

    abstract::The incidence of obesity, with its impact on the development of comorbidities, including diabetes and cardiovascular disease, represents one of the greatest global health threats of the 21st century. This is particularly damning considering the vast progress that has been made in understanding the factors and molecula...


    pub_type: 杂志文章,评审


    authors: Perez-Tilve D

    更新日期:2017-05-01 00:00:00

  • Interactions of dopamine and neurotensin on calcium fluxes and prolactin release in normal rat pituitary cells.

    abstract::We studied the role of calcium in dopaminergic control of the neuroendocrine effects of neurotensin. In primary cultures of dispersed normal female rat anterior pituitary cells the interactions of dopamine and neurotensin were examined with reference to the rate of PRL release, the magnitude of 45Ca2+ uptake, the rate...


    pub_type: 杂志文章


    authors: Login IS,Kuan SI,Judd AM,MacLeod RM

    更新日期:1990-10-01 00:00:00

  • Molecular characterization and in situ localization of murine endoglin reveal that it is a transforming growth factor-beta binding protein of endothelial and stromal cells.

    abstract::Endoglin is an integral membrane glycoprotein predominantly expressed on human endothelial cells and recently shown to bind transforming growth factor-beta 1 (TGF beta 1) with high affinity. We now report the cloning and sequencing of a full-length murine endoglin complementary DNA of 2902 base pairs which hybridizes ...


    pub_type: 杂志文章


    authors: St-Jacques S,Cymerman U,Pece N,Letarte M

    更新日期:1994-06-01 00:00:00

  • Prostaglandin E2-induced up-regulation of c-fos messenger ribonucleic acid is primarily mediated by 3',5'-cyclic adenosine monophosphate in MC3T3-E1 osteoblasts.

    abstract::The mechanism by which the proto-oncogene, c-fos, is up-regulated in response to PGE2 in the mouse osteoblastic (MC3T3-E1) cell line was investigated using RT-PCR. c-fos messenger RNA up-regulation by dmPGE2 is rapid, starting 10 min post stimulation, and transient. The specific protein kinase A (PKA) inhibitor, H89, ...


    pub_type: 杂志文章


    authors: Fitzgerald J,Dietz TJ,Hughes-Fulford M

    更新日期:2000-01-01 00:00:00

  • The protein kinase-C activation domain of the parathyroid hormone.

    abstract::The PTH activates both adenylate cyclase and a mechanism that increases membrane-associated protein kinase-C (PKC) activity. To define the hormone's PKC activation domain we have used a panel of PTH fragments and ROS 17/2 rat osteosarcoma cells as the target cells. PTH equally and maximally increased PKC activity in R...


    pub_type: 杂志文章


    authors: Jouishomme H,Whitfield JF,Chakravarthy B,Durkin JP,Gagnon L,Isaacs RJ,MacLean S,Neugebauer W,Willick G,Rixon RH

    更新日期:1992-01-01 00:00:00

  • Fetal programming: prenatal testosterone treatment causes intrauterine growth retardation, reduces ovarian reserve and increases ovarian follicular recruitment.

    abstract::Exposure to testosterone (T) during d 30-90 of fetal life results in low-birth-weight offspring, hypergonadotropism, multifollicular ovaries, and early cessation of cyclicity. The multifollicular phenotype may result from failure of follicles to regress and consequent follicular persistence or, alternatively, increase...


    pub_type: 杂志文章


    authors: Steckler T,Wang J,Bartol FF,Roy SK,Padmanabhan V

    更新日期:2005-07-01 00:00:00

  • A primary cell culture system of luteinizing hormone releasing hormone neurons derived from embryonic olfactory placode in the rhesus monkey.

    abstract::The purpose of this study is to establish a primary LHRH cell culture system using embryonic olfactory placode and to examine whether LHRH cells derived from olfactory placode and the migratory pathway of LHRH neurons mature in vitro. Six monkey fetuses at the ages of E34-E36 were delivered surgically and the area inc...


    pub_type: 杂志文章


    authors: Terasawa E,Quanbeck CD,Schulz CA,Burich AJ,Luchansky LL,Claude P

    更新日期:1993-11-01 00:00:00

  • A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins.

    abstract::A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed "leukocytic endogenous mediator" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model ami...


    pub_type: 杂志文章


    authors: Wannemacher RW Jr,Pekarek RS,Thompson WL,Curnow RT,Beall FA,Zenser TV,DeRubertis FR,Beisel WR

    更新日期:1975-03-01 00:00:00

  • Identification of novel factors that regulate GnRH gene expression and neuronal migration.

    abstract::We used differential display PCR on two GnRH producing cell lines to identify genes involved in GnRH gene expression and neuronal migration. RNA from Gn10 cells (derived from a tumor in the olfactory area when GnRH neurons are migrating and make low levels of GnRH) and from GT1-7 cells (derived from a tumor in forebra...


    pub_type: 杂志文章


    authors: Fang Z,Xiong X,James A,Gordon DF,Wierman ME

    更新日期:1998-08-01 00:00:00

  • Expression of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 in pancreatic beta-Cells and its role in promotion of insulin secretion and protection against diabetes.

    abstract::Insulin secretion by beta-cells of pancreatic islets is regulated by various soluble factors including glucose and hormones. The importance of direct cell-cell communication among beta-cells or between beta-cells and other cell types for such regulation has remained unclear, however. Transmembrane proteins Src homolog...


    pub_type: 杂志文章


    authors: Kobayashi M,Ohnishi H,Okazawa H,Murata Y,Hayashi Y,Kobayashi H,Kitamura T,Matozaki T

    更新日期:2008-11-01 00:00:00

  • Inhibin suppresses luteinizing hormone (LH)-releasing hormone self-priming: direct action on follicle-stimulating hormone secretion and opposition of estradiol-enhanced LH secretion.

    abstract::Previous studies have suggested that the ovary produces a factor that maintains the pituitary in a state of low LHRH responsiveness that must be overcome by the self-priming action of LHRH. To determine the role of inhibin in maintaining low LHRH responsiveness in pituitaries of diestrous female rats, endogenous inhib...


    pub_type: 杂志文章


    authors: Culler MD

    更新日期:1992-03-01 00:00:00

  • Oxyntomodulin inhibits food intake in the rat.

    abstract::Oxyntomodulin is derived from proglucagon processing in the intestine and the central nervous system. To date, no role in the central nervous system has been demonstrated. We report here that oxyntomodulin inhibits refeeding when injected intracerebroventricularly and into the hypothalamic paraventricular nucleus of 2...


    pub_type: 杂志文章


    authors: Dakin CL,Gunn I,Small CJ,Edwards CM,Hay DL,Smith DM,Ghatei MA,Bloom SR

    更新日期:2001-10-01 00:00:00

  • Decreased thyroidal response to thyrotropin in diabetic mice.

    abstract::The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased ...


    pub_type: 杂志文章


    authors: Bagchi N,Brown TR,Shivers B,Lucas S,Mack RE

    更新日期:1981-11-01 00:00:00

  • Effects of progesterone and tamoxifen on glucocorticosteroid-induced egg-white protein synthesis in the chick oviduct.

    abstract::A single injection of either natural (cortisol, corticosterone) or synthetic [dexamethasone (DEX), triamcinolone acetonide] glucocorticosteroids to estradiol-primed, withdrawn chicks, resulted in a dose-dependent increase in the relative rates of ovalbumin and conalbumin synthesis. The simultaneous injection of equal ...


    pub_type: 杂志文章


    authors: Le Bouc Y,Groyer A,Cadepond F,Groyer-Schweizer G,Robel P,Baulieu EE

    更新日期:1985-06-01 00:00:00

  • Up-regulation of advanced glycated products receptors in the brain of diabetic rats is prevented by antioxidant treatment.

    abstract::Diabetics have at least twice the risk of stroke and may show performance deficit in a wide range of cognitive domains. The mechanisms underlying this gradually developing end-organ damage may involve both vascular changes and direct damage to neuronal cells as a result of overproduction of superoxide by the respirato...


    pub_type: 杂志文章


    authors: Aragno M,Mastrocola R,Medana C,Restivo F,Catalano MG,Pons N,Danni O,Boccuzzi G

    更新日期:2005-12-01 00:00:00

  • Medial prefrontal cortical estradiol rapidly alters memory system bias in female rats: ultrastructural analysis reveals membrane-associated estrogen receptors as potential mediators.

    abstract::High plasma levels of estradiol (E2) are associated with use of a place memory system over a response memory system. We examined whether infusing estradiol into the medial prefrontal cortex (mPFC) or anterior cingulate cortex (AC) could affect memory system bias in female rats. We also examined the ultrastructural dis...


    pub_type: 杂志文章


    authors: Almey A,Cannell E,Bertram K,Filardo E,Milner TA,Brake WG

    更新日期:2014-11-01 00:00:00

  • Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptor-mediated iodide efflux and phosphoinositide turnover in FRTL-5 cells.

    abstract::Exposure of FRTL-5 thyroid cells to ATP (1 microM to 1 mM) resulted in the stimulation of I- efflux in association with the induction of inositol trisphosphate production and intracellular Ca2+ mobilization. Nonhydrolyzable ATP derivatives, ADP and GTP, were also as effective in magnitude as ATP, whereas neither AMP n...


    pub_type: 杂志文章


    authors: Okajima F,Sho K,Kondo Y

    更新日期:1988-08-01 00:00:00

  • Transactivation of the parathyroid hormone promoter by specificity proteins and the nuclear factor Y complex.

    abstract::We previously identified a highly conserved specificity protein 1 (Sp1) DNA element in mammalian PTH promoters that acted as an enhancer of gene transcription and bound Sp1 and Sp3 proteins present in parathyroid gland nuclear extracts. More recently, a nuclear factor (NF)-Y element (NF-Y(prox)) was also described by ...


    pub_type: 杂志文章


    authors: Alimov AP,Park-Sarge OK,Sarge KD,Malluche HH,Koszewski NJ

    更新日期:2005-08-01 00:00:00

  • Selective estrogen receptor modulators differentially regulate Alzheimer-like changes in female 3xTg-AD mice.

    abstract::Estrogen-based hormone therapy (HT) in postmenopausal women may reduce the risk of Alzheimer's disease (AD), although HT remains controversial. One key concern with HT is the potential of adverse outcomes such as breast and uterine cancer. A promising strategy to maximize HT benefits and minimize HT risks is the use o...


    pub_type: 杂志文章


    authors: Carroll JC,Pike CJ

    更新日期:2008-05-01 00:00:00

  • Bfk, a novel member of the bcl2 gene family, is highly expressed in principal cells of the mouse epididymis and demonstrates a predominant nuclear localization.

    abstract::B-cell lymphoma 2 (BCL2) family kin (BFK) is a recently identified novel protein that is similar to proteins of the BCL2 family. In the present study, we discovered that the mouse Bfk transcript is expressed at the highest level in the epididymis. Two transcripts of 0.9 and 2.6 kb in size were identified, with alterna...


    pub_type: 杂志文章


    authors: Pujianto DA,Damdimopoulos AE,Sipilä P,Jalkanen J,Huhtaniemi I,Poutanen M

    更新日期:2007-07-01 00:00:00

  • Reticulocyte cytosol activator protein: effects on the stimulatory and inhibitory regulatory proteins of adenylate cyclase.

    abstract::Rat reticulocytes contain a cytosol activator protein (RCAP) that augments hormone-sensitive adenylate cyclase activity in the rat reticulocyte and other systems. In a previous publication, using a highly purified preparation of RCAP, we reported that the stimulatory guanine nucleotide-binding protein (Ns) was require...


    pub_type: 杂志文章


    authors: Shane E,Yeh M,Feigin AS,Owens JM,Bilezikian JP

    更新日期:1985-07-01 00:00:00

  • Lack of effect of vitamin D and its metabolites on intestinal phosphate transport in familial hypophosphatemia of mice.

    abstract::Intestinal calcium and phosphate transport was studied in normal and hypophosphatemic mice fed a variety of dietary regimens with and without vitamin D. Regardless of dietary phosphorus levels, the genetic hypophosphatemic mice had drastically reduced levels of serum inorganic phosphate and intestinal phosphate transp...


    pub_type: 杂志文章


    authors: O'Doherty PJ,DeLuca HF,Eicher EM

    更新日期:1977-10-01 00:00:00

  • ER and PR in renomedullary interstitial cells during Syrian hamster estrogen-induced tumorigenesis: evidence for receptor-mediated oncogenesis.

    abstract::The estrogen-induced and -dependent Syrian hamster renal tumor is the most intensively studied model in estrogen carcinogenesis. Yet, it remains confounding that the kidney of this species behaves as an estrogen target tissue. As both reproductive and urinary systems arise from the same germinal ridge, we propose that...


    pub_type: 杂志文章


    authors: Li JJ,Weroha SJ,Davis MF,Tawfik O,Hou X,Li SA

    更新日期:2001-09-01 00:00:00