Glucocorticoid resistant syndromes--molecular basis and clinical presentations.


:The mechanisms of action of glucocorticoid hormones are mediated via specific intracellular receptor proteins. The glucocorticoid receptor (GR) regulates expression of specific target genes or gene networks by ligand-dependent transcriptional activation, i.e. ligand-dependent activation of the receptor with subsequent dimer formation and DNA binding. There are a number of factors, such as the receptor concentration, receptor associated proteins, receptor alterations and the effects on the gene network including hormonal regulation of transcription, mRNA splicing and translation, that might influence glucocorticoid responsiveness in a normal and healthy population as well as in different diseases. Several categories of glucocorticoid resistance have been described including inherited GR resistance which has been explained in terms of specific mutations and offers an important model for genetic and clinical studies of steroid sensitivity, and relative glucocorticoid resistance, which occurs naturally in the course of cellular differentiation, cell to cell or tissue to tissue, since all cells possess receptors for glucocorticoids but do not show the same response to them. From a clinical point of view, it is also interesting to consider preexisting genetic susceptibility to glucocorticoids, acquired changes in the GR gene structure and organization, including alterations of noncoding sequences, and the importance of mutations, deletions and other changes in the GR gene affecting receptor function. Analysis of mutations within the receptor resulting in relative glucocorticoid resistance, both generalized inherited glucocorticoid resistance (GIGR) and directed mutagenesis, has identified two regions of clustered mutations in the proximity of previously identified affinity labeled residues directly affecting the steroid binding function. Finally, studies of New Words primates and cell lines derived from hematologic malignancies constitute animal and human models for the molecular basis of glucocorticoid resistance where a number of inherited and acquired mutations in the GR gene have been demonstrated.


J Neuroendocrinol


Brönnegård M,Stierna P,Marcus C




Has Abstract


1996-06-01 00:00:00












  • Changes in the expression of corticotrophin-releasing hormone, mineralocorticoid receptor and glucocorticoid receptor mRNAs in the hypothalamic paraventricular nucleus induced by fornix transection and adrenalectomy.

    abstract::The paraventricular nucleus (PVN) in the hypothalamus receives inputs from the hippocampus The present study explored the influence of the hippocampus on genes mediating glucocorticoid feedback in the PVN. Accordingly, the expression of mRNAs for corticotrophin-releasing hormone (CRH), the mineralocorticoid receptor (...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Han F,Ozawa H,Matsuda KI,Lu H,De Kloet ER,Kawata M

    更新日期:2007-04-01 00:00:00

  • Effect of short-and long-term gonadectomy on neuroactive steroid levels in the central and peripheral nervous system of male and female rats.

    abstract::Significant levels of neuroactive steroids are still detected in the nervous system of rodents after the removal of peripheral steroidogenic glands. However, the influence of the plasma levels of gonadal steroids on the levels of neuroactive steroids in the nervous system has not so far been clarified in detail. Accor...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Caruso D,Pesaresi M,Maschi O,Giatti S,Garcia-Segura LM,Melcangi RC

    更新日期:2010-11-01 00:00:00

  • Brain processing of duodenal and portal glucose sensing.

    abstract::Peripheral and central glucose sensing play a major role in the regulation of food intake. Peripheral sensing occurs at duodenal and portal levels, although the importance of these sensing sites is still controversial. The present study aimed to compare the respective influence of these sensing pathways on the eating ...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Boubaker J,Val-Laillet D,Guérin S,Malbert CH

    更新日期:2012-08-01 00:00:00

  • Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.

    abstract::The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Li SY,Li XF,Hu MH,Shao B,Poston L,Lightman SL,O'Byrne KT

    更新日期:2014-08-01 00:00:00

  • Interactions between opioid peptides and adrenaline-containing neurons modulate luteinizing hormone secretion in male rats.

    abstract::Abstract There is increasing evidence that the opioid inhibition of luteinizing hormone (LH) secretion is mediated, at least in part, by catecholaminergic mechanisms. This study determined the effects of selective manipulation of noradrenergic and adrenergic systems on the ability of opiate receptor blockade to induce...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Martensz ND,Goldstone AP,Stuart E,Everitt BJ

    更新日期:1990-02-01 00:00:00

  • Post-transcriptional regulation of the gonadotropin-releasing hormone gene in GT1-7 cells.

    abstract::GT1-7 cells respond to treatment with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), with an inhibition of transcription of the proGnRH gene and decreases in GnRH mRNA levels. However, the timing of this decrease in GnRH mRNA levels suggests that a decrease in GnRH mRNA stability may be involved in addition...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Gore AC,Yeo TT,Ho A,Roberts JL

    更新日期:1997-04-01 00:00:00

  • Vasopressin antisense oligonucleotide induces temporary diabetes insipidus in rats.

    abstract::The purpose of this study was to downregulate the transcriptional message of arginine vasopressin (AVP) by antisense treatment. A complete phosphorothioate antisense oligodesoxynucleotide corresponding to the beginning of the coding region of rat AVP mRNA was constructed and injected into the lateral ventricle of rats...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


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    更新日期:1994-04-01 00:00:00

  • Sympathoadrenal system differentially affects photoperiodic changes in humoral immunity of Siberian hamsters (Phodopus sungorus).

    abstract::Siberian hamsters (Phodopus sungorus) rely on photoperiod as a primary cue to coordinate seasonally appropriate changes in physiology and behaviour. Among these seasonal changes is reduced immune function in short 'winter-like' days, compared to long 'summer-like' days. Previous evidence suggests that immune function ...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Demas GE,Drazen DL,Jasnow AM,Bartness TJ,Nelson RJ

    更新日期:2002-01-01 00:00:00

  • The median eminence detects and responds to circulating prolactin in the male mouse.

    abstract::In addition to its established lactational roles, prolactin acts on multiple target tissues and its circulating levels are responsive to a range of physiological stimuli. The present study used immunohistochemistry to demonstrate that systemic administration of prolactin activates target cells in the arcuate nucleus a...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Kirk SE,Grattan DR,Bunn SJ

    更新日期:2019-06-01 00:00:00

  • Involvement of Cholecystokinin in Food Intake: II. Lactational Hyperphagia in the Rat.

    abstract::Abstract The role of Cholecystokinin in the hyperphagia of lactation was studied by measuring the concentration of this hormone in plasma and cerebrospinal fluid in relation to food intake in lactating rats. Cholecystokinin was measured by high-performance liquid chromatography and radioimmunoassay in plasma and by ra...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


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    更新日期:1990-12-01 00:00:00

  • Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats.

    abstract::Women are twice as likely to suffer from mood disorders than men. Moreover, a growing body of evidence suggests a reciprocal modulation between sex steroids and the serotonin (5-HT) system. A previous study from our laboratory has shown that the progesterone metabolites 5beta-pregnane-3,20-dione (5beta-DHP) and 5alpha...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Robichaud M,Debonnel G

    更新日期:2005-03-01 00:00:00

  • Prostaglandin E2 acts via the hypothalamus to stimulate ACTH secretion in the fetal sheep.

    abstract::Prostaglandin (PG) E2 is secreted into the fetal circulation during late gestation in the sheep. Exogenous infusion of PGE2 is associated with robust increases in the circulating concentrations of ACTH and cortisol and it has therefore been proposed that endogenous PGE2 modulates the activity of the fetal HPA axis, wh...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Young IR,Loose JM,Kleftogiannis F,Canny BJ

    更新日期:1996-09-01 00:00:00

  • Seasonal variation of melatonin binding sites in the pars tuberalis of the male mink (Mustela vison).

    abstract::The seasonal changes of 2-[125I]iodomelatonin binding were studied using quantitative autoradiography in the pars tuberalis (PT) of the mink, a short-day breeder, kept out of doors. Studies were performed at 7 times of the year (July, September, October, January, February, and May), corresponding to different states o...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Messager S,Caillol M,George D,Martinet L

    更新日期:1997-07-01 00:00:00

  • Peripheral endocannabinoid system-mediated actions of rimonabant on growth hormone secretion are ghrelin-dependent.

    abstract::The somatotroph axis is a crucial pathway regulating metabolism. Despite the fact that the endocannabinoid system has been also revealed as a potent modulator of energy homeostasis, little information is available concerning a putative interaction between these two systems. The aim of the present study was to determin...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Al-Massadi O,Gabellieri E,Trujillo ML,Señaris R,Pagotto U,Pasquali R,Casanueva FF,Seoane LM

    更新日期:2010-11-01 00:00:00

  • Expression of corticotropin releasing factor (CRF), urocortin and CRF type 1 receptors in hypothalamic-hypophyseal systems under osmotic stimulation.

    abstract::The expression of corticotropin releasing factor (CRF) and urocortin in hypothalamic magnocellular neurones increases in response to osmotic challenge. To gain a better understanding of the physiological roles of CRF and urocortin in fluid homeostasis, CRF, urocortin and CRF type 1 receptor (CRFR-1) gene expression wa...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Imaki T,Katsumata H,Miyata M,Naruse M,Imaki J,Minami S

    更新日期:2001-04-01 00:00:00

  • The neuroactive steroid 5 alpha-tetrahydrodeoxycorticosterone increases GABAergic postsynaptic inhibition in rat neocortical neurons in vitro.

    abstract::The neuroactive steroid 5 alpha-pregnane-3 alpha, 21-diol-20-one (5 alpha-tetrahydrodeoxycorticosterone; 5 alpha-THDOC) has been shown to potentiate GABA-induced chloride currents in cell cultures and subcellular preparations. In this study, we recorded from pyramidal neurons in an in vitro slice preparation of the ad...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Teschemacher A,Zeise ML,Holsboer F,Zieglgänsberger W

    更新日期:1995-03-01 00:00:00

  • Estrogen-sensitive oxytocin binding sites are differently regulated by progesterone in the telencephalon and the hypothalamus of the rat.

    abstract::The localization at the cellular level and the regulation by progesterone of the estrogen-sensitive oxytocin binding sites was studied in the rat telencephalon and the hypothalamus by using quantitative film-autoradiography and histoautoradiography. Male rats (castrated or not) and ovariectomized females (estradiol su...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Krémarik P,Freund-Mercier MJ,Stoeckel ME

    更新日期:1995-04-01 00:00:00

  • Isolation and structure-bioactivity characterization of glycosylated N-pro-opiomelanocortin isoforms.

    abstract::The N-terminal fragment of mouse pro-opiomelanocortin (N-POMC) was isolated from AtT-20 cell-conditioned medium on the basis of immunoreactivity to an anti-POMC1-50 monoclonal antibody by a concentration step, a cation exchange step, reversed phase high-performance liquid chromatography (HPLC) and size exclusion HPLC....

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Lu J,Swinnen E,Proost P,De Vreese B,Vankelecom H,Denef C

    更新日期:2002-11-01 00:00:00

  • Preterm labour: tsunami waves?

    abstract::Preterm labour and birth can be delayed but are generally unstoppable, threatening the health of the mother-baby duo. This may be a result of peripheral signals prematurely recruiting the oxytocin neurones that co-ordinate the timing of birth and, via specialised activity and secretion patterns, drive uterine contract...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Douglas AJ

    更新日期:2010-09-01 00:00:00

  • Neonatal programming by neuroimmune challenge: effects on responses and tolerance to septic doses of lipopolysaccharide in adult male and female rats.

    abstract::A mild immune challenge experienced during the neonatal period leads to attenuated febrile responses to a similar challenge experienced later in life. However, the immune response to an endotoxin differs depending upon the severity of the challenge and it is not clear whether a neonatal immune challenge will also affe...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Spencer SJ,Field E,Pittman QJ

    更新日期:2010-04-01 00:00:00

  • Dorsal hippocampal administration of triiodothyronine enhances long-term memory for trace cued and delay contextual fear conditioning in rats.

    abstract::Thyroid hormones play critical roles in brain maturation and cognitive functions. The present study investigated the role of thyroid hormone in emotional learning and memory using trace and delay contextual and cued fear conditioning tasks, respectively. Rats were administered triiodothyronine (T3) into the dorsal hip...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Sui L,Wang F,Liu F,Wang J,Li BM

    更新日期:2006-11-01 00:00:00

  • Opioid receptor subtypes involved in the regulation of prolactin secretion during pregnancy and lactation.

    abstract::Afferent endogenous opioid neuronal systems facilitate prolactin secretion in a number of physiological conditions including pregnancy and lactation, by decreasing tuberoinfundibular dopamine (TIDA) inhibitory tone. The aim of this study was to investigate the opioid receptor subtypes involved in regulating TIDA neuro...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Andrews ZB,Grattan DR

    更新日期:2003-03-01 00:00:00

  • Effects of chronic bromocriptine treatment on tyrosine hydroxylase (TH) mRNA expression, TH activity and median eminence dopamine concentrations in ageing rats.

    abstract::The purpose of this study was to investigate the age-related changes in the responsiveness of tuberoinfundibular dopamine (TIDA) neurones to chronic hypoprolactinemia induced by treatment with bromocriptine, a dopamine receptor agonist. In one experiment, TIDA neuronal activity after acute hypoprolactinemia or exogeno...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: MohanKumar PS,MohanKumar SM,Quadri SK,Voogt JL

    更新日期:2001-03-01 00:00:00

  • Circadian variation of plasma calcitonin gene-related Peptide in man.

    abstract::Abstract Calcitonin gene-related peptide (CGRP) is one of the most potent endogenous vasodilator peptides known so far. Almost all clinical studies using or measuring CGRP are conducted during the day, and hence this study was carried out to see any variations of CGRP levels in the circulation during this period. Thre...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Wimalawansa SJ

    更新日期:1991-06-01 00:00:00

  • Kisspeptin and the preovulatory gonadotrophin-releasing hormone/luteinising hormone surge in the ewe: basic aspects and potential applications in the control of ovulation.

    abstract::The identification of the neural mechanisms controlling ovulation in mammals has long been a 'holy grail' over recent decades, although the recent discovery of the kisspeptin systems has totally changed our views on this subject. Kisspeptin cells are the major link between gonadal steroids and gonadotrophin-releasing ...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章,评审


    authors: Caraty A,Franceschini I,Hoffman GE

    更新日期:2010-07-01 00:00:00

  • Vasopressin Expression in Cultured Neurons is Stimulated by Cyclic AMP.

    abstract::Abstract Vasopressin and oxytocin genes are expressed in mutually exclusive sets of magnocellular neurons in the hypothalamus. Cell specificity and regulation are probably controlled by extra- and intracellular signals acting on one or the other gene. In order to identify factors that regulate peptide expression, we h...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Ceding P,Schilling K,Schmale H

    更新日期:1990-12-01 00:00:00

  • Development of gonadotrophs and thyrotrophs in the female foetal sheep pituitary: immunocytochemical localization studies.

    abstract::In order to investigate the ontogenesis of cell types in the pituitary gland, anterior pituitaries were collected from female foetal sheep at days 70, 100 and 130 of gestation (term = 145 days). Cells containing the common alpha-subunit and the specific beta-subunits of luteinizing hormone (LH), follicle-stimulating h...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Thomas GB,McNeilly AS,Brooks AN

    更新日期:1993-04-01 00:00:00

  • Increased expression of type 1 angiotensin II receptors in the hypothalamic paraventricular nucleus following stress and glucocorticoid administration.

    abstract::Double staining in situ hybridization studies have shown that angiotensin II (AII) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN) are located primarily in corticotropin releasing hormone (CRH) neurons of the parvicellular subdivision. The purpose of these studies was to investigate the role o...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Aguilera G,Kiss A,Luo X

    更新日期:1995-10-01 00:00:00

  • Effects of restraint stress and spontaneous hypertension on neuropeptide Y neurones in the brainstem and arcuate nucleus.

    abstract::Neuropeptide Y (NPY) is found in autonomic neurones and participates in regulation of autonomic functions. To investigate the role of NPY in the stress response in normo- and hypertensive rats, activation of brainstem and arcuate nucleus (ARC) NPY neurones and levels of NPY mRNA in the ARC were measured in response to...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Krukoff TL,MacTavish D,Jhamandas JH

    更新日期:1999-09-01 00:00:00

  • Noradrenergic nuclei that receive sensory input during mating and project to the ventromedial hypothalamus play a role in mating-induced pseudopregnancy in the female rat.

    abstract::In female rats, vaginal-cervical stimulation (VCS) received during mating induces bicircadian prolactin surges that are required for the maintenance of pregnancy or pseudopregnancy (PSP). The neural circuits that transmit VCS inputs to the brain have not been fully described, although mating stimulation is known to ac...

    journal_title:Journal of neuroendocrinology

    pub_type: 杂志文章


    authors: Northrop LE,Polston EK,Erskine MS

    更新日期:2010-10-01 00:00:00