Glucocorticoid sensitivity in fibromyalgia patients: decreased expression of corticosteroid receptors and glucocorticoid-induced leucine zipper.
In fibromyalgia (FM) patients, differences in glucocorticoid receptor (GR) affinity and disturbances associated with loss of hypothalamic-pituitary-adrenal (HPA) axis resiliency have been observed. Based on these studies, we investigated whether FM would be associated with abnormalities in glucocorticoid (GC) sensitivity. Salivary and blood samples were collected from 27 FM patients and 29 healthy controls. Total plasma cortisol and salivary free cortisol were quantified by ELISA and time-resolved fluorescence immunoassay, respectively. GR sensitivity to dexamethasone was evaluated through IL-6 inhibition in stimulated whole blood. The corticosteroid receptors, GR alpha and mineralocorticoid receptor, as well as the glucocorticoid-induced leucine zipper (GILZ) and the FK506 binding protein 5 mRNA expression were assessed in peripheral blood mononuclear cells (PBMCs) by real-time RT-PCR. Furthermore, the corticosteroid receptors were analysed for polymorphism. We observed lower basal plasma cortisol levels (borderline statistical significance) and a lower expression of corticosteroid receptors and GILZ in FM patients when compared to healthy controls. The MR rs5522 (I180V) minor allele was found more often in FM patients than in controls and this variant was recently associated with a mild loss of receptor function. The lower GR and MR expression and possibly the reduced MR function may be associated with an impaired function of the HPA axis in these patients which, compounded by lower anti-inflammatory mediators, may sustain some of symptoms that contribute to the clinical picture of the syndrome.
Macedo
Joana A
JA
Institute of Immunology, Laboratoire National de Santé, 20A rue Auguste Lumière, L-1011, Luxembourg.
Hesse
Judith
J
Turner
Jonathan D
JD
Meyer
Jobst
J
Hellhammer
Dirk H
DH
Muller
Claude P
CP
D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005356:Fibromyalgia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics*; D012463:Saliva / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics*
D005938:Glucocorticoids; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone; D006854:Hydrocortisone