Quantification of type I and II adrenal steroid receptors in neuronal, lymphoid and pituitary tissues.
Circulating lymphocytes are frequently used to study glucocorticoid receptor (GR) regulation in various clinical disease states, such as depression. Since little is known about the relationship between lymphoid and neuronal GR, type II adrenal steroid receptors (i.e., GR) were quantitated in neuronal (hippocampus, frontal cortex, hypothalamus), lymphoid (circulating lymphocytes, spleen, thymus) as well as pituitary tissues of adrenal-intact and 1 day adrenalectomized (ADX) rats using the selective type II receptor ligand, [3H]RU 28362. Specific, high affinity (dissociation constant = 0.2-0.3 nM) type II receptors were present in all tissues examined with the density in 1 day ADX rats being thymus greater than frontal cortex = spleen greater than hippocampus = pituitary greater than hypothalamus greater than lymphocytes. Adrenal intact rats had fewer type II receptors in frontal cortex, hippocampus and spleen as compared to 1 day ADX rats. Dose-response competition studies using [3H]RU 28362 and various unlabelled steroids revealed a binding profile indicative of a type II receptor with the potency being RU 28362 greater than triamcinolone acetonide greater than dexamethasone = corticosterone much greater than aldosterone in both whole brain and spleen soluble fractions. In contrast to the high concentration of type II receptors in the various tissues, the density of type I (i.e., mineralocorticoid) receptors was very low or nondetectable in the same tissues of 1 day ADX rats with the notable exception of the hippocampus where there were approximately comparable levels of both receptors. These results document the widespread distribution of type II adrenal steroid receptors in neuronal and lymphoid tissues which are similar in affinity and steroid specificity.
Lowy
M T
MT
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
D000732:Androstanols / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003907:Dexamethasone / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D000732:Androstanols; D011965:Receptors, Glucocorticoid; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone