Research ArticleMetabolism

ABCC1 confers tissue-specific sensitivity to cortisol versus corticosterone: A rationale for safer glucocorticoid replacement therapy

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Science Translational Medicine  17 Aug 2016:
Vol. 8, Issue 352, pp. 352ra109
DOI: 10.1126/scitranslmed.aaf9074

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A kinder, gentler steroid

In some clinical situations, such as congenital adrenal hyperplasia, it is necessary to suppress endogenous adrenal function by blocking the secretion of the adrenocorticotropic hormone from the brain. Usually, cortisol is used for this purpose, but cortisol doses large enough to achieve adrenal suppression are problematic because they cause metabolic adverse effects. Nixon et al. have identified another steroid, corticosterone, as offering a better solution for this treatment scenario. Because of the differences in the expression patterns of transporters that export each steroid out of cells, corticosterone is more effectively retained in brain cells, where it is needed, and less likely to be retained in adipose tissue, where it would cause side effects.