title: Glucocorticoid receptor alpha and beta isoforms are not mutated in bipolar affective disorder.
abstract: The periodically hyperactive hypothalamic-pituitary-adrenal (HPA) axis in bipolar affective disorders, as well as the reported changes in the binding characteristics of the glucocorticoid receptor (GR), suggest the possible involvement of the GR in the aetiopathology of this disease. This was investigated by screening the coding sequences of both GR isoforms, GRalpha and GRbeta, for the presence of mutations. As a genetic predisposition has been implicated, we included in this study bipolar patients who were siblings. By RT-PCR of peripheral blood mononuclear cells from patients suffering from bipolar illness, using primers spanning the whole length of the GRalpha and GRbeta coding region and subsequent agarose gel electrophoresis, heteroduplex and sequence analyses, no GR mutations could be detected. Since glucocorticoid receptor activity can be modulated by agents other than the respective ligand (eg by growth factors, cytokines and stress signals), our results favor derangements in the modulation of GR activity by such agents and not in the primary structure of the receptor as aetiopathologic factors of bipolar disease.
authors.affiliation: Laboratory of Biological Chemistry, University of Athens Medical School, 75 Mikras Asias Str, GR-115 27 Goudi, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Moutsatsou
authors.forename: A
authors.initials: A
authors.lastname: Tsolakidou
authors.forename: G
authors.initials: G
authors.lastname: Trikkas
authors.forename: C
authors.initials: C
authors.lastname: Troungos
authors.forename: C E
authors.initials: CE
authors.lastname: Sekeris
mesh_terms: D000328:Adult; D000339:Affect; D000368:Aged; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta