Differences in Corticosterone and Dexamethasone Binding to Rat Brain and Pituitary¹

Abstract

In an attempt to relate binding of 3H-corticosterone and 3H-dexamethasone to their respective potencies in blocking pituitary-adrenal activity, cytosol binding in vitro and cell nuclear binding both in vivo and in tissue slices in vitro were studied in hippocampus, hypothalamus, and anterior pituitary of adrenalectomized rats. It was found that the extremely potent glucocorticoid dexamethasone has a different pattern of binding than corticosterone in the brain and in the anterior pituitary. 1) In cytosol, differences in the estimated binding capacities in a particular tissue for 3H-corticosterone and 3H-dexamethasone and different rates of inactivation in the ability to bind the two steroids are observed. 2) For 3H-corticosterone, cytosol binding in hippocampus is higher than that in hypothalamus, and cell nuclear binding follows the same pattern. For 3H-dexamethasone, cytosol binding is again higher in the hippocampus than in hypothalamus but cell nuclear binding in the two structures is not significantly different. With respect to the anterior pituitary, binding to cell nuclei is higher for 3H-dexamethasone, while the binding to cytosol macromolecules is higher for 3H-corticosterone. 3) In vivo and in vitro cell nuclear binding for both steroids showed the same pattern among the three tissues, but in vivo data showed more distinctly the preference of 3H-dexamethasone for the anterior pituitary and the preference of 3H-corticosterone for the hippocampus. 4) When labeled in tissue slices, cell nuclear radioactivity appears to be bound to macromolecules. 5) Steroid metabolism does not occur in slices during 60 min in vitro at 25 C and cannot account for the observed tissue differences in binding. The existence of more than one population of corticosteroid-binding sites in brain and in anterior pituitary is suggested. The results are consistent with the view that the dexamethasone blockade of stress-induced ACTH release is mediated by the anterior pituitary, while the high specificity of cotricosterone binding in the hippocampus implies a specific but as yet undetermined effect of the hormone in this brain area, an effect which may not be directly related to regulation of ACTH secretion.

Characterization of Glucocorticoid Type II Receptors in Neuronal and Glial Cultures from Rat Brain

“…These ['HIDEX binding sites display similar characteristics to those found in brain (13,32), optic nerve glia (33), C6 glioma cells (1 [8][9][10][11][12][13][14][15][16][17][18][19][20] and other glucocorticoid target organs (8,34 (35)(36)(37)(38)(39)(40). Strong immunofluorescent staining has been observed in the hippocampus, hypothalamus, lateral septum, raphe nuclei, ventromedial tegmentum, locus coeruleus, nucleus of solitary tract and area postrema (35)(36)(37)(38)(39)(40).…”

Glucocorticoids exacerbate hypoxia-induced expression of the pro-apoptotic gene Bnip3 in the developing cortex

“…Previous reports indicate that DEX entry into the CNS is hindered by P-glycoprotein product at the blood brain barrier (Meijer et al, 1998). Furthermore, it has been shown that DEX alters HPA axis regulation at the level of the anterior pituitary (de Kloet et al, 1974, De Kloet et al, 1975. Based on these reports and our experimental design we are unable to conclude if DEX in vivo regulates Bnip3 directly at the level of the cortex and hippocampus or indirectly through HPA axis dysregulation.…”

Childhood trauma and dimensions of depression: a specific association with the cognitive domain

“…28 This association of item and context then leads to the phenomenological experience of recollection, which is a mental faculty pertaining to the cognitive sphere of brain functioning. Glucocorticoid receptors are richly expressed in the hippocampus, 29 and hippocampal volume loss is well documented in chronic stress, 30 in animal models of exogenous glucocorticoid administration, 31 and in patients with Cushing syndrome. 32 Adrenal glucocorticoids usually display adaptive effects in the short run, but contribute to pathophysiology in the presence either of repeated stress or of HPA axis deregulation (allostatic overload).…”