REGULATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY BY THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE RAT

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) inactivates glucoc orticoids and thereby modulates their access to both mineralocorticoid and glucocorticoid receptors. Since 11 beta-OHSD activity influences the biological responses of the hypothalamic-pituitary-adrenal axis, i t might be regulated by components of this axis. We examined 11 beta-O HSD activity in adrenalectomized rats treated for 9 days with dexameth asone and with or without ACTH. Adrenalectomy and low-dose (2 mu g/day ) dexamethasone had no effect on 11 beta-OHSD activity in renal cortex , hippocampus or heart, and reduced enzyme activity in aorta. High-dos e dexamethasone (50 mu g/day) had no effect in renal cortex but increa sed enzyme activity by at least 50% in all other sites. This effect of dexamethasone was unaffected by the co-administration of ACTH. We als o examined the metabolism of dexamethasone by 11 beta-OHSD in homogeni zed rat tissues. Only in kidney, in the presence of NAD rather than NA DP, was dexamethasone converted to a more polar metabolite previously identified as 11-dehydrodexamethasone. We conclude that: dexamethasone induction of 11 beta-OHSD is tissue-specific, and includes vascular t issues and hippocampus but not kidney; this tissue-specificity may be explained by contrasting metabolism of dexamethasone by the isoforms o f 11 beta-OHSD; fluctuations of glucocorticoid levels within the physi ological range may not have a biologically significant effect on 11 be ta-OHSD activity; and the inhibitory effect of ACTH, observed previous ly in humans, is Likely to depend on the presence of intact adrenal gl ands.