Increased levels of glucocorticoid receptors and enhanced glucocorticoid receptor auto-regulation after hydrocortisone challenge in B-lymphoblastoids from patients with affective disorders.
The stress response is mediated by a negative feedback effect of glucocorticoids on corticosteroid receptors. Here, we examine the potential contribution of these receptors and their response to a glucocorticoid challenge to dysfunctions of the hypothalamic-pituitary-adrenal axis reported for patients with affective disorders. In a pilot-study, we established B-lymphoblastoid cell lines from patients suffering from affective disorders and healthy subjects and measured the quantity of glucocorticoid receptors at steady state conditions after 12-weeks cell culture. After short-term incubation with 0.1 microM hydrocortisone for 48 h, the decrease of glucocorticoid receptors was also investigated. After 12-weeks cell culture, we found a significantly higher number of cytosolic glucocorticoid receptors in B-lymphoblastoids from patients (B(max)=804.9+/-342.5 fmol/mg protein) compared to those from healthy subjects (B(max)=576.9+/-190.3 fmol/mg protein: p=0.045; t-test). The increase of the glucocorticoid receptor level in the group of patients could be attributed largely to the higher number of these receptors measured in B-lymphoblastoids of patients suffering from major depressive disorder. The in vitro regulation of glucocorticoid receptors in response to 0.1 microM hydrocortisone for 48 h resulted in a significantly larger decrease in cultures of B-lymphoblastoids derived from patients (to 32.9+/-7.5%) than in those from healthy subjects (to 45.8+/-8.2%). The stronger decrease of glucocorticoid receptors in the group of patients (p=0.0001; t-test) was independent of the duration of illness and medication, suggesting a trait-like characteristic of the response.
Henning
Uwe
U
Neurobiochemical Research Unit, Department of Psychiatry, Heinrich-Heine-University Duesseldorf, Bergische Landstrasse 2, D-40629 Duesseldorf, Germany. uwe.henning@lvr.de
Krieger
Klaus
K
Loeffler
Stefan
S
Rivas
Fabio
F
Orozco
Guillermo
G
de Castro
Manuel G
MG
Rietschel
Marcella
M
Noethen
Markus M
MM
Klimke
Ansgar
A
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001714:Bipolar Disorder / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D003865:Major Depressive Disorder / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011869:Radioligand Assay; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone