by Aaron Gochman (’18)

Most pharmacological approaches in the study of congenital adrenal hyperplasia involve the administration of corticosteroids, potent drugs that quickly affect the body. Extended use of corticosteroids, however, typically yields unpleasant metabolic side effects. Despite this weakness, corticosteroids have been the mainstream treatment in attempting to suppress adrenal androgen. However, scientists from the United Kingdom have discovered a novel approach: corticosterone, a steroid that confers tissue-specific sensitivity.

Corticosterone is exported through membrane transporter ABCC1. ABCC1 is different from other ABC-family membrane transporters in that it only exports corticosterone and not cortisol or other common corticosteroids that produce metabolic side effects. Hence the team inhibited ABCC1 in mice to accumulate corticosterone levels and not those of other corticosteroids.

To test the validity of these results in humans, the team treated patients with Addison’s disease with corticosterone with the aim of suppressing adrenocorticotropic hormone (ACTH). The results from the trial found that subcutaneous adipose levels of corticosterone were lower than those of cortisol, a potent corticosteroid. These data imply that corticosterone represents a safer alternative as a steroid therapy.

References:

1. M. Nixon, et al., ABCC1 confers tissue-specific sensitivity to cortisol versus corticosterone: A rationale for safer glucocorticoid replacement therapy. Sci Transl Med 8, (2016).