Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain.
The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stress-activated circuitry, which suggest that these sites are responsive to glucocorticoid feedback. The intracellular localization of GR-ir was examined in CA1 and CA2 pyramidal neurons of the hippocampus. In intact rats GR-ir is predominantly present in the cell nucleus. Adrenalectomy (ADX) caused a slow depletion of the GR-ir signal from the cell nucleus until near detection limits at two weeks postsurgery. At that time, 1 h after administration to longterm ADX rats the synthetic glucocorticoid (type 2) agonist RU 28362 as well as a moderate and high dose of corticosterone (CORT) markedly enhanced the cell nuclear GR-ir. The type 2 antagonist RU 38486 also caused an increase of GR immunostaining in cell nuclei upon acute administration to ADX rats. The mineralocorticoid aldosterone (ALDO) and a low dose of CORT, which bind almost exclusively to type 1 corticosteroid receptors, were ineffective. In conclusion, our data suggest that in the hippocampal CA1-2 neurons type 1 and type 2 corticosteroid receptors may coexist. The steroid-induced changes in cell nuclear immunoreactive GR staining intensity suggest possible cytoplasmic-cell nuclear translocation of GR and/or exposure of immunogenic GR domains.
van Eekelen
J A
JA
Rudolf Magnus Institute for Pharamcology, Medical Faculty, University of Utrecht, The Netherlands.
Kiss
J Z
JZ
Westphal
H M
HM
de Kloet
E R
ER
D000818:Animals; D001923:Brain Chemistry; D001933:Brain Stem / Q000032:analysis; D006624:Hippocampus / Q000032:analysis; D007158:Immunologic Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000032:analysis*
D011965:Receptors, Glucocorticoid