Whilst topical steroids represent one of the most frequently administered treatments for skin and hair diseases, predominantly based on their glucocorticoid receptor-mediated anti-inflammatory effects, the mineralocorticoid effects of topical steroids have received surprisingly little attention. However, the role of mineralocorticoid receptor (MR) signaling is now known to extend beyond the kidney, with human skin, including the hair follicle (HF), expressing the MR. Using microdissected female HFs treated ex vivo with MR agonists and antagonists, we sought to determine the effects of MR-mediated signaling in the cutaneous context. Indeed, not only did the skin and HF epithelium express the MR at both the gene and protein level, but its expression was hair cycle dependent. Moreover, the selective MR antagonist eplerenone promoted hair shaft elongation and hair matrix keratinocyte proliferation whilst delaying catagen (HF regression). These novel observations suggest that the female human HF is sensitive to the inhibition of MR signaling and provide the first evidence that sustained MR signaling may even be required to maintain the growth phase (anagen) of human scalp HFs. Indeed, these data encourage the systematic evaluation of MR agonists and antagonists in human hair growth control so as to identify much-needed, novel anti-hirsutism and/or hair growth-promoting agents, respectively.
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