hrp0089fc1.4 | Adrenals & HPA Axis | ESPE2018

Whole Exome Sequencing in Patients with Primary Generalized Glucocorticoid Resistance Identifies a Novel TRIM28 Gene Mutation (p.R230X)

Sertedaki Amalia , Marinakis Nikos , Nicolaides Nicolas C. , Crousos George , Charmandari Evangelia

Introduction: Primary Generalized Glucocorticoid Resistance or Chrousos syndrome (CS) is a rare sporadic or familial disorder characterized by generalized, partial tissue insensitivity to glucocorticoids. Mutations of the NR3C1 gene, which encodes the human glucocorticoid receptor, have been identified in many but not all patients with CS.Objective: To identify novel genes related to CS in patients without NR3C1 gene mutations.<p cl...

hrp0082p1-d2-2 | Adrenals &amp; HP Axis | ESPE2014

Functional Characterization of a Novel Heterozygous Point Mutation in the Human Glucocorticoid Receptor Gene Causing Primary Generalized Glucocorticoid Resistance

Nicolaides Nicolas C , Vlachakis Dimitris , Sertedaki Amalia , Kossida Sophia , Chrousos George P , Charmandari Evangelia

Background: Primary generalized glucocorticoid resistance (PGGR) or Chrousos syndrome is a rare familial or sporadic condition caused by mutations in the hGR gene, which reduce tissue sensitivity to glucocorticoids. A new case of PGGR caused by a novel heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand-binding domain of the receptor, was recently reported in a patient with an adre...

hrp0086rfc1.1 | Adrenals | ESPE2016

Tracing the Glucocorticoid Receptor Evolutionary Pedigree: Insights from a Comprehensive Phylogenetic Analysis of the Full NR Super-Family

Vlachakis Dimitrios , Nicolaides Nicolas C. , Papageorgiou Louis , Lamprokostopoulou Agaristi , Charmandari Evangelia

Background: The nuclear receptor (NR) family comprises three main subfamilies: the steroid hormones receptors, the thyroid/retinoid hormone receptors and the orphan receptors. Proteins within the NR family share common domain architecture. These closely related receptors and their cognate ligand compounds play a key role in homeostasis, reproduction, growth and development. Despite their biological significance, their evolution and diversification remains to be elucidated....

hrp0089fc1.5 | Adrenals &amp; HPA Axis | ESPE2018

Untargeted Plasma Metabolomics in Subjects with Differences in Tissue Glucocorticoid Sensitivity Identifies a Novel metabolic Signature

Nicolaides Nicolas C. , Ioannidi Maria-Konstantina , Koniari Eleni , Sertedaki Amalia , Klapa Maria I. , Chrousos George P. , Charmandari Evangelia

Background: Tissue glucocorticoid sensitivity is characterized by a considerable variation in terms of therapeutic response and side effects to synthetic glucocorticoids. The multi-metabolite concentration profile measured by untargeted plasma metabolomics provides a comprehensive metabolic signature that might be used in clinical practice.Objective and Hypotheses: To investigate the usefulness of plasma metabolomics in identifying a metabolic signature ...

hrp0086fc1.2 | Adrenals | ESPE2016

Transcriptomic Analysis in Healthy Subjects with Differences in Tissue Sensitivity to Glucocorticoids Identifies Novel Disease-associated Genes

Nicolaides Nicolas C. , Polyzos Alexandros , Koniari Eleni , Lamprokostopoulou Agaristi , Golfinopoulou Eleni , Papathanasiou Chryssanthi , Sertedaki Amalia , Thanos Dimitris , Charmandari Evangelia

Background: Glucocorticoids exert profound immune-modulating effects and regulate the expression of genes involved in cell cycle progression and apoptosis. Synthetic glucocorticoids are the most potent agents used in the treatment of inflammatory, autoimmune and lymphoproliferative disorders. Considerable variation in response to therapeutic doses of glucocorticoids exists among individuals, as evidenced by differences both in disease response and in the incidence of glucocort...

hrp0086p1-p483 | Fat Metabolism and Obesity P1 | ESPE2016

The Effectiveness of a Stress Management Intervention Program in the Management of Overweight and Obesity in Childhood and Adolescence

Stavrou Stavroula , Nicolaides Nicolas C. , Papageorgiou Ifigeneia , Papadopoulou Pinelopi , Terzioglou Eleni , Darviri Christina , Chrousos George P. , Charmandari Evangelia

Background: Obesity in childhood and adolescence represents a major health problem of our century, and accounts for a significant increase in morbidity and mortality in adulthood. In addition to the increased consumption of calories and lack of exercise, accumulating evidence suggests that childhood obesity is strongly associated with prolonged and excessive activation of the stress system.Objective and hypotheses: The aim of our study was to assess the ...

hrp0082fc1.1 | Adrenal | ESPE2014

Molecular mechanisms of nongenomic glucocorticoid actions: the role of human glucocorticoid receptor S-palmitoylation

Nicolaides Nicolas C , Roberts Michael L , Kino Tomoshige , Katsantoni Eleni , Sertedaki Amalia , Chrousos George P , Charmandari Evangelia

Background: In humans, glucocorticoids (GCs) regulate a broad spectrum of physiologic functions, exerting both genomic and nongenomic actions through their ubiquitously expressed glucocorticoid receptor (hGR). The rapid nongenomic actions of GCs are likely to be mediated by membrane hGRs that transduce the glucocorticoid signal via activation of kinases. S-palmitoylation plays an important role in plasma membrane localization and occurs through a highly conserved nine amino ac...

hrp0082p2-d1-373 | Fat Metabolism &amp; Obesity | ESPE2014

Expression Levels of the Growth-Arrest-Specific Transcript 5 in Overweight and Obese Children and Adolescents

Fragouli Terpsihori , Sertedaki Amalia , Farakla Ioanna , Nicolaides Nicolas C , Dracopoulou Maria , Papassotiriou Ioannis , Chrousos George P , Charmandari Evangelia

Background: The noncoding RNA growth-arrest-specific transcript 5 (Gas5) is abundant in cells whose growth has been arrested owing to lack of nutrients or growth factors. Gas5 is a riborepressor of the glucocorticoid receptor, influencing cell survival and metabolic activities during starvation by inhibiting the latter’s transcriptional activity.Aim: To determine the expression levels of Gas5 in blood samples of obese, overweight and lean children a...

hrp0082p3-d2-774 | Fat Metabolism &amp; Obesity (1) | ESPE2014

The Prevalence of 25-Hydroxyvitamin D Insufficiency and Deficiency Among Overweight and Obese Children and Adolescents in Greece

Giannios Christos , Farakla Ioanna , Papadopoulos Georgios , Bakopoulou Ioanna , Nicolaides Nicolas C , Papathanasiou Chryssanthi , Drakopoulou Maria , Chrousos George P , Charmandari Evangelia

Background: The prevalence of obesity has increased dramatically in Greece in the last decades, and more than 30% of children and adolescents are currently overweight or obese. Obesity is associated with decreased circulating 25-hydroxyvitamin D concentrations, which might predispose to metabolic syndrome and cardiovascular morbidity and mortality.Objective and hypotheses: To determine serum 25-hydroxyvitamin D concentrations and their relationship to ca...

hrp0084p2-168 | Adrenals | ESPE2015

The Natural Mutant Receptor hGRαT556I Causes Primary Generalised Glucocorticoid Resistance Through Decreased Affinity for the Ligand and Impaired Interaction with the GRIP1 Coactivator

Nicolaides Nicolas C , Skyrla Eirini , Vlachakis Dimitrios , Psarra Anna-Maria G , Sertedaki Amalia , Kossida Sophia , Charmandari Evangelia

Background: Primary generalised glucocorticoid resistance (PGGR) is a rare condition characterised by tissue insensitivity to glucocorticoids owing to inactivating mutations of the hGR gene. A new case of PGGR was reported in a patient with an adrenal incidentaloma harboring a novel heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 of the receptor.Objec...