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Stress Down-Regulates Corticosterone Receptors in a Site-Specific Manner in the Brain^*

ROBERT M. SAPOLSKY, LEWIS C. KREY and BRUCE S. McEWEN

Laboratory of Neuroendocrinology, The Rockefeller University New York, New York 10021

Address requests for reprints to: Dr. Lewis C. Krey, Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, New York 10021.

Abstract

We have examined whether corticosterone receptor number within the brain can be regulated by its own ligand and whether such autoregulation reduces receptor number after the sustained secretion of corticosterone during repeated stress. Glucocorticoid receptors were measured in cytosolic preparations from acutely adrenalectomized rats using [1,2,6,7-³H] dexamethasone; maximal binding and receptor affinity parameters were determined by Scatchard analysis.

Sustained elevations of circulating corticosterone, whether by repeated stress or exogenous corticosterone administration, did not change receptor affinity for [³H] dexamethasone, but significantly reduced cytosolic corticosterone receptor number. This reduction in total receptor number could not be attributed to residual tissue contamination with endogenous corticosterone after adrenalectomy or to translocation of cystosolic receptors to cell nuclei. The receptor reductions were anatomically specific, occurring in the hippocampus and amygdala, but not in the hypothalamus or pituitary, and were limited, in that exogenous corticosterone plus stress reduced receptor number no more than did stress alone. Further, 3 weeks of daily administration of 5 mg corticosterone caused reductions similar to those seen after only 4 days of treatment. Finally, the declines in glucocorticoid receptor number were reversible; receptor concentrations returned to normal levels within 1 week after the cessation of treatment with exogenous corticosterone. Thus, this study presents evidence that glucocorticoid down-regulation may constitute a physiological phenomenon. (Endocrinology 114: 287, 1984)

Footnotes

^* Rats were provided by the National Institute on Aging through a grant to R.M.S.

Irma T. Hirschl Career Scientist.

Received May 31, 1983.

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