Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

Abstract:

:Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Sefton C,Harno E,Davies A,Small H,Allen TJ,Wray JR,Lawrence CB,Coll AP,White A

doi

10.1210/en.2016-1571

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

4257-4265

issue

11

eissn

0013-7227

issn

1945-7170

journal_volume

157

pub_type

杂志文章
  • Two distinct effects of recombinant human tumor necrosis factor-alpha on osteoclast development and subsequent resorption of mineralized matrix.

    abstract::The multifunctional cytokine tumor necrosis factor-alpha (TNF alpha) stimulates osteoclastic resorption. It is not known which steps in osteoclast formation are affected by TNF alpha. We have investigated the effects of recombinant human TNF alpha (rhTNF alpha) on osteoclast development and osteoclastic resorption in ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-129-3-1596

    authors: van der Pluijm G,Most W,van der Wee-Pals L,de Groot H,Papapoulos S,Löwik C

    更新日期:1991-09-01 00:00:00

  • Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin.

    abstract::In vitro addition of rat insulin (200, 400 or 800 muU/ml) to collagenase-isolated pancreatic islets of adult rats diminished glucose (3 mg/ml)-induced insulin release which was correlated with a decrease of the ratio of total NADPH/NADP and inhibition of glucose oxidation via the pentose phosphate shunt (PPS). NADH an...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-99-6-1469

    authors: Ammon HP,Verspohl E

    更新日期:1976-12-01 00:00:00

  • Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing.

    abstract::Lefty/Ebaf polypeptides, novel members of the TGF-beta superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form. Here, we show that decidual differentiation of endom...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0684

    authors: Tang M,Mikhailik A,Pauli I,Giudice LC,Fazelabas AT,Tulac S,Carson DD,Kaufman DG,Barbier C,Creemers JW,Tabibzadeh S

    更新日期:2005-12-01 00:00:00

  • Immunocytochemical localization of cytochromes P450 17 alpha-hydroxylase and aromatase in embryonic cell layers of elongating porcine blastocysts.

    abstract::Localized expression of cytochromes P450 17 alpha-hydroxylase (P450c17) and aromatase (P450arom) was investigated in embryonic cell layers of elongating porcine blastocysts by immunocytochemistry. Blastocysts were flushed from the uterus on day 12 of pregnancy, fixed in paraformaldehyde, embedded in paraffin, sectione...

    journal_title:Endocrinology

    pub_type: 更正并重新发布的文章,杂志文章

    doi:10.1210/endo.135.6.7988410

    authors: Conley AJ,Christenson LK,Ford SP,Christenson RK

    更新日期:1994-12-01 00:00:00

  • Angiotensin II and cyclic adenosine 3',5'-monophosphate induce human steroidogenic acute regulatory protein transcription through a common steroidogenic factor-1 element.

    abstract::Steroidogenic acute regulatory protein (StAR) synthesis and steroidogenesis are stimulated by activation of divergent signaling pathways in the adrenal cortex. The two major physiological regulators of aldosterone synthesis in the adrenal zona glomerulosa are angiotensin II (AII) and extracellular K+, which both media...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.140.10.7085

    authors: Clark BJ,Combs R

    更新日期:1999-10-01 00:00:00

  • Studies on the in vitro cytotoxic effect of amiodarone.

    abstract::Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may be responsible for both complications, but a cytotoxic effect of the drug on the thyroid resulting in thyroiditis has been reported. In the present study t...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.134.5.8156930

    authors: Chiovato L,Martino E,Tonacchera M,Santini F,Lapi P,Mammoli C,Braverman LE,Pinchera A

    更新日期:1994-05-01 00:00:00

  • Characterization of the atrial natriuretic peptide system in the oviduct.

    abstract::The atrial natriuretic peptide (ANP) gene is expressed in several extraatrial tissues in which ANP may be involved in the regulation of autocrine or paracrine functions. In the ovary, the synthesis of ANP, its binding sites, and a physiological role were found. The ANP system in the oviduct, however, is yet to be defi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.6.5160

    authors: Kim SH,Cho KW,Kim SZ,Koh GY

    更新日期:1997-06-01 00:00:00

  • Regulation of overgrowth and expression of prostatic binding protein in rat chimeric prostate gland.

    abstract::Enlargement of the chimeric ventral prostate gland (VP) was induced by directly implanting either fetal urogenital sinus mesenchyme (UGM) or intact fetal urogenital sinus (UGS) into the VP of intact adult rats. The macromolecular content in the chimeric prostate increased from 40-100% (UGM implants) to 200-300% (UGS i...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-118-6-2437

    authors: Thompson TC,Chung LW

    更新日期:1986-06-01 00:00:00

  • Tumor necrosis factor-alpha inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures.

    abstract::Tumor necrosis factor-alpha (TNF alpha), a product of activated monocytes, induces tissue wasting in certain solid tumors in vivo and in in vitro model systems. Recent studies indicate that TNF alpha also regulates cell replication and expression of differentiated function in a variety of nonneoplastic cell systems. S...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-123-3-1442

    authors: Centrella M,McCarthy TL,Canalis E

    更新日期:1988-09-01 00:00:00

  • Neonatal estrogen exposure disrupts uterine development in the postnatal sheep.

    abstract::Postnatal development of the ovine uterus between birth and postnatal day (PND) 56 involves budding differentiation of the endometrial glandular epithelium from the luminal epithelium (LE) followed by extensive coiling and branching morphogenesis of the tubular glands. To determine the short- and long-term effects of ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-0178

    authors: Hayashi K,Carpenter KD,Spencer TE

    更新日期:2004-07-01 00:00:00

  • Cellular localization of the growth hormone binding protein in the rat.

    abstract::In the rat a GH-binding protein (GHBP) exists that is derived from the GH receptor gene by an alternative messenger RNA splicing mechanism such that the transmembrane and intracellular domains of the GH receptor are replaced by a hydrophilic carboxy terminus. Previous immunohistochemical studies detailing the localiza...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.130.5.1374020

    authors: Lobie PE,García-Aragón J,Wang BS,Baumbach WR,Waters MJ

    更新日期:1992-05-01 00:00:00

  • Testosterone and dihydrotestosterone concentrations in plasma, epididymal tissues, and seminal fluid of adult rats.

    abstract::The concentration of testosterone (T) and 5alpha-dihydrotestosterone (DHT) in plasma, seminal fluid, and epididymis of male Wistar rats have been determined by radioimmunoassay. The DHT/T ratio rose from 0.1 in blood to 1 in testicular fluid and 4 in epididymal fluid. This ratio is 2 in tissues of "caput" epididymis a...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-98-1-111

    authors: Pujol A,Bayard F,Louvet JP,Boulard C

    更新日期:1976-01-01 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...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-96-3-651

    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

  • alpha-Fetoprotein and transcortin behave as acute phase reactants in the maternal and fetal compartments of the inflammatory pregnant mouse.

    abstract::Immunological and binding methods have been used to demonstrate that acute inflammation induced in the pregnant mouse by a single sc turpentine injection elicits plasma protein responses in the fetal as well as in the maternal compartment. The maternal response involves, along with the classical pattern of positive an...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-120-5-1782

    authors: Vranckx R,Savu L,Maya M,Nunez EA

    更新日期:1987-05-01 00:00:00

  • Serum growth hormone and prolactin during and after the development of the obese-hyperglycemic syndrome in mice.

    abstract::Mice with the recessively inherited obese-hyperglycemic syndrome (ob/ob) and their nonobese litter mates were studied over a 26-week period. The body weights and serum glucose levels of ob/ob mice began to rise markedly at 5-6 weeks of age and remained elevated throughout the period of study. Obese mice were significa...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-98-1-139

    authors: Larson BA,Sinha YN,Vanderlaan WP

    更新日期:1976-01-01 00:00:00

  • The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics.

    abstract::A side population (SP) has been identified in a number of tissues, where it typically represents a small population enriched in stem/progenitor cells. In this study we show that the adult mouse anterior pituitary (AP) also contains a characteristic SP displaying verapamil-sensitive Hoechst dye efflux capacity. A major...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0185

    authors: Chen J,Hersmus N,Van Duppen V,Caesens P,Denef C,Vankelecom H

    更新日期:2005-09-01 00:00:00

  • Arginine vasopressin triggers intracellular calcium release, a calcium-activated potassium current and exocytosis in identified rat corticotropes.

    abstract::Arginine vasopressin (AVP) stimulates the secretion of ACTH from pituitary corticotropes. We investigated the action of AVP in single corticotropes of male rats. Corticotropes were identified with the reverse hemolytic plaque assay using antibodies against ACTH. Using the whole-cell recording technique in conjunction ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.5.5999

    authors: Tse A,Lee AK

    更新日期:1998-05-01 00:00:00

  • The antigonadotropic actions of prostaglandin F2 alpha and phorbol ester are mediated by separate processes in rat luteal cells.

    abstract::Protein kinase-C (PKC) has been suggested as a possible mediator of the antigonadotropic action of prostaglandin F2 alpha (PGF2 alpha) in luteal cells. To examine this possibility, we evaluated the effects of phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] in relation to those of PGF2 alpha on cAMP accumula...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-3-1388

    authors: Musicki B,Aten RF,Behrman HR

    更新日期:1990-03-01 00:00:00

  • Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes.

    abstract::The PTH and PTH-related protein (PTHrP) system consists of two hormones, at least two G protein-coupled seven-transmembrane domain receptors, and at least two intracellular signal transduction pathways for each receptor. The PTH/PTHrP receptor is present in the conventional target tissues of PTH action, namely kidney ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.10.8828480

    authors: Behar V,Nakamoto C,Greenberg Z,Bisello A,Suva LJ,Rosenblatt M,Chorev M

    更新日期:1996-10-01 00:00:00

  • Three high threshold calcium channel subtypes in rat corticotropes.

    abstract::In this study on highly enriched populations of cultured rat corticotropes, Ca2+ channel inhibitors were used to identify subtypes of the high threshold Ca2+ channel current under voltage clamp conditions. From a holding potential (-50 mV) that eliminated the low threshold T-type current, 52 +/- 4% of the total curren...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.136.9.7649100

    authors: Kuryshev YA,Childs GV,Ritchie AK

    更新日期:1995-09-01 00:00:00

  • Peroxisome proliferator-activated receptor-alpha activation during pregnancy attenuates glucose-stimulated insulin hypersecretion in vivo by increasing insulin sensitivity, without impairing pregnancy-induced increases in beta-cell glucose sensing and res

    abstract::We investigated the effects of acute (24-h) peroxisome proliferator-activated receptor (PPAR)alpha activation by WY14,643 (pirinixic acid) treatment on glucose-stimulated insulin secretion (GSIS) during pregnancy, in the rat, in relation to insulin sensitivity. GSIS after iv glucose challenge (500 mg/kg) was increased...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-220811

    authors: Sugden MC,Greenwood GK,Smith ND,Holness MJ

    更新日期:2003-01-01 00:00:00

  • Nuclear factor-kappaB activates transcription of the androgen receptor gene in Sertoli cells isolated from testes of adult rats.

    abstract::The androgen receptor (AR) in Sertoli cells mediates the actions of testosterone on spermatogenesis. However, the transcription factors responsible for AR gene regulation in Sertoli cells remain unknown. In this study, we determined that nuclear factor-kappaB (NF-kappaB) regulates transcription of AR in primary cultur...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-0987

    authors: Zhang L,Charron M,Wright WW,Chatterjee B,Song CS,Roy AK,Brown TR

    更新日期:2004-02-01 00:00:00

  • Solubilization, purification, and partial characterization of thyrotropin receptor from bovine and human thyroid glands.

    abstract::In an attempt to purify the thyroid receptor for TSH and to study interaction with the thyroid-stimulating antibody (TSAb) of graves' disease, we used both bovine and human thyroid glands. With either tissue, the 10,000 X g pellet of homogenized material was solubilized with 0.5% Triton N-101; excess Triton was remove...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-110-4-1381

    authors: Koizumi Y,Zakarija M,McKenzie JM

    更新日期:1982-04-01 00:00:00

  • Bone Regulation of Insulin Secretion and Glucose Homeostasis.

    abstract::For centuries our image of the skeleton has been one of an inert structure playing a supporting role for muscles and a protective role for inner organs like the brain. Cell biology and physiology modified this view in the 20st century by defining the constant interplay between bone-forming and bone resorbing cells tha...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endocr/bqaa149

    authors: Ducy P

    更新日期:2020-10-01 00:00:00

  • Differential expression of A- and B-subtypes of cholecystokinin/gastrin receptors in the developing calf pancreas.

    abstract::Cholecystokinin (CCK)/gastrin receptors were characterized in calf pancreatic plasma membranes from newborns, 28- and 119-day-old milk-fed preruminants, and 119-day-old weaned ruminants. Scatchard analysis of [125I]Bolton-Hunter reagent-[Thr28,Nle31]CCK-(25-33) binding indicated two classes of binding sites: high affi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.133.3.8365360

    authors: Le Meuth V,Philouze-Rome V,Le Huerou-Luron I,Formal M,Vaysse N,Gespach C,Guilloteau P,Fourmy D

    更新日期:1993-09-01 00:00:00

  • Uterine insulin-like growth factor-I receptors: regulation by estrogen and variation throughout the estrous cycle.

    abstract::This study was undertaken to identify uterine insulin-like growth factor-I (IGF-I) receptors and examine the regulation of these receptors throughout the estrous cycle and after 17 beta-estradiol (E2) administration to immature rats. We have demonstrated type I IGF receptors in crude uterine membranes by binding and c...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-125-2-597

    authors: Ghahary A,Murphy LJ

    更新日期:1989-08-01 00:00:00

  • Acute intravenous corticotropin-releasing factor administration: effects on insulin secretion in lean and genetically obese fa/fa rats.

    abstract::The effect of an i.v. administration of different doses (250, 500, and 1000 pmol) of ovine CRF (oCRF) on plasma glucose and insulin levels in lean and genetically obese fa/fa rats was investigated. In both phenotypes, i.v. CRF promoted a rapid (peak at 1 min) transient doubling of basal insulin levels without a concom...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.130.4.1312430

    authors: Rohner-Jeanrenaud F,Jeanrenaud B

    更新日期:1992-04-01 00:00:00

  • Pituitary adenylate cyclase-activating polypeptide regulates prolactin promoter activity via a protein kinase A-mediated pathway that is independent of the transcriptional pathway employed by thyrotropin-releasing hormone.

    abstract::The hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), can efficiently increase cAMP levels in pituitary cells and release a number of pituitary hormones, suggesting an important physiological role for this peptide in pituitary function. Exposure of GH3 rat pituitary cells to PACAP resul...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.4.8625900

    authors: Coleman DT,Chen X,Sassaroli M,Bancroft C

    更新日期:1996-04-01 00:00:00

  • Evidence for regulation of peptide-YY release by the proximal gut.

    abstract::Peptide-YY (PYY) is a novel enteric peptide that is structurally related to pancreatic polypeptide and neuropeptide-Y. The objectives of the present experiments were to characterize the following aspects of PYY metabolism: the distribution of PYY in the canine gastrointestinal tract, the release of PYY in response to ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-3-1438

    authors: Greeley GH Jr,Jeng YJ,Gomez G,Hashimoto T,Hill FL,Kern K,Kurosky T,Chuo HF,Thompson JC

    更新日期:1989-03-01 00:00:00

  • Lateral Hypothalamic Area Neurotensin Neurons Are Required for Control of Orexin Neurons and Energy Balance.

    abstract::The lateral hypothalamic area (LHA) is essential for motivated ingestive and locomotor behaviors that impact body weight, yet it remains unclear how the neurochemically defined subpopulations of LHA neurons contribute to energy balance. In particular, the role of the large population of LHA neurotensin (Nts) neurons h...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2018-00311

    authors: Brown J,Sagante A,Mayer T,Wright A,Bugescu R,Fuller PM,Leinninger G

    更新日期:2018-09-01 00:00:00