Long-term lack of endogenous glucocorticoids down-regulates glucocorticoidreceptor levels in the rat forebrain

To understand the effect of a chronic lack of endogenous glucocorticoids on glucocorticoid receptor levels, the changes of glucocorticoid receptor con tent in the rat forebrain five months after adrenalectomy were investigated . In the long-term adrenalectomized rats that showed a hormone deficiency a nd loss of glucocorticoid receptor immunoreactivity in the forebrain, an in traperitoneal injection of corticosterone was used to elevate the serum hor mone levels and recover glucocorticoid receptor immunoreactivity in the for ebrain. One hour later, when the blood corticosterone returned to the norma l level, the recovery of glucocorticoid receptor immunoreactivity in the fo rebrain was examined by immunohistochemistry. Since the complete restoratio n of glucocorticoid receptor immunoreactivity was shown to depend on the pr esence of normal levels of both serum hormone and intracellular glucocortic oid receptors, the weak reappearance of glucocorticoid receptor immunoreact ivity in any forebrain area of the long-term adrenalectomized rats that had normal serum corticosterone might reflect the low intracellular glucocorti coid receptor levels there. Our results revealed a weak reappearance of glu cocorticoid receptor immunoreactivity in some forebrain areas of the long-t erm adrenalectomized rats after corticosterone treatment; the hippocampal g ranule cell layer and cerebral cortex in particular showed very weak recove ry of glucocorticoid receptor immunoreactivity. Conversely, neurons in the CA1/CA2 subfields of the hippocampal pyramidal cell layer, immediately adja cent to the granule cell layer on the same brain section, exhibited a stron g reappearance of glucocorticoid receptor immunoreactivity, to near normal levels. These results suggest that, five months after adrenalectomy, the intracellu lar glucocorticoid receptor content decreased in the rat granule cell layer and cerebral cortex. Therefore, the long-term lack of endogenous glucocort icoids after adrenalectomy might down-regulate but not up-regulate the intr acellular glucocorticoid receptor level, and the presence of glucocorticoid s is important for the continued synthesis of glucocorticoid receptors. (C) 1999 IBRO. Published by Elsevier Science Ltd.