Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use

2015 ◽  
Vol 174 (11) ◽  
pp. 1421-1431 ◽  
Author(s):  
Ozlem Cavkaytar ◽  
Dogus Vuralli ◽  
Ebru Arik Yilmaz ◽  
Betul Buyuktiryaki ◽  
Ozge Soyer ◽  
...  
Keyword(s):  
Hypothalamic Pituitary Adrenal Axis ◽  
High Dose ◽  
Inhaled Corticosteroid ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

Regulation of 11β-hydroxysteroid dehydrogenase activity by the hypothalamic-pituitary-adrenal axis in the rat

1994 ◽  
Vol 141 (3) ◽  
pp. 467-472 ◽  
Author(s):  
B R Walker ◽  
B C Williams ◽  
C R W Edwards
Keyword(s):  
Enzyme Activity ◽  
Glucocorticoid Receptors ◽  
Renal Cortex ◽  
Hydroxysteroid Dehydrogenase ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
High Dose ◽  
Rat Tissues ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

Abstract 11β-Hydroxysteroid dehydrogenase (11β-OHSD) inactivates glucocorticoids and thereby modulates their access to both mineralocorticoid and glucocorticoid receptors. Since 11β-OHSD activity influences the biological responses of the hypothalamic-pituitary-adrenal axis, it might be regulated by components of this axis. We examined 11β-OHSD activity in adrenalectomized rats treated for 9 days with dexamethasone and with or without ACTH. Adrenalectomy and low-dose (2 μg/day) dexamethasone had no effect on 11β-OHSD activity in renal cortex, hippocampus or heart, and reduced enzyme activity in aorta. High-dose dexamethasone (50 μg/day) had no effect in renal cortex but increased enzyme activity by at least 50% in all other sites. This effect of dexamethasone was unaffected by the co-administration of ACTH. We also examined the metabolism of dexamethasone by 11β-OHSD in homogenized rat tissues. Only in kidney, in the presence of NAD rather than NADP, was dexamethasone converted to a more polar metabolite previously identified as 11-dehydrodexamethasone. We conclude that: dexamethasone induction of 11β-OHSD is tissue-specific, and includes vascular tissues and hippocampus but not kidney; this tissue-specificity may be explained by contrasting metabolism of dexamethasone by the isoforms of 11β-OHSD; fluctuations of glucocorticoid levels within the physiological range may not have a biologically significant effect on 11β-OHSD activity; and the inhibitory effect of ACTH, observed previously in humans, is likely to depend on the presence of intact adrenal glands. Journal of Endocrinology (1994) 141, 467–472

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