The ATP-binding cassette proteins ABCC1 and ABCB1 as modulators of glucocorticoid action

Devine, K; Villalobos, E; Kyle, CJ; Andrew, R; Reynolds, RM; Stimson, RH; Nixon, M; Walker, BR

doi:10.1038/s41574-022-00745-9

The ATP-binding cassette proteins ABCC1 and ABCB1 as modulators of glucocorticoid action

Lookup NU author(s): Dr Elisa Villalobos Villegas ORCiD, Professor Brian Walker ORCiD

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This is the authors' accepted manuscript of a review published in its final definitive form in 2022. For re-use rights please refer to the publishers terms and conditions.

Abstract

Responses to hormones that act through nuclear receptors are controlled by modulating hormone concentrations not only in the circulation but also within target tissues. The role of enzymes that amplify or reduce local hormone concentrations has become well-established for glucocorticoid and other lipophilic hormones; moreover, transmembrane transporters have proven critical in determining tissue responses to thyroid hormones. However, there has been less consideration of the role of transmembrane transport for steroid hormones. ATP-binding cassette (ABC) proteins were first shown to influence the accumulation of glucocorticoids in cells almost three decades ago, but observations over the past ten years suggest that differential transport propensities of both exogenous and endogenous glucocorticoids by ABCB1 and ABCC1 transporters provides a mechanism whereby different tissues are preferentially sensitive to different steroids. This Review summarises this evidence and the new insights provided for the physiology and pharmacology of glucocorticoid action, including new approaches to glucocorticoid replacement.