Why steroids may not always work in alopecia areata: Elevated unoccupied glucocorticoid receptors and decreased levels of thioredoxin

Alopecia areata (AA) patients show a variable response in hair regrowth with glucocorticoid (GC) steroid treatment. The biochemical mechanisms by which GCs stimulate hair growth in patients with AA is unknown, yet clinicians commonly use topical, intralesional, and even oral GC steroid therapy to treat AA. In this study, scalp biopsy specimens were obtained from 15 patients (in each group) with extensive AA, male androgenetic alopecia (AGA), and normal controls (N), and were analyzed for GC receptor (GCR) content. All patients were off therapy at the time they were studied. Tissue samples were assessed for total, occupied, and unoccupied GCR type I and II binding. Results from patients with AA show that the type II GCR is elevated and in an unoccupied state compared to AGA and N patient biopsies (p < 0.01). A factor known to activate the GCR, called thioredoxin (TR), was decreased in AA scalp compared to N and AGA (p < 0.01). Finding elevated unoccupied type II GCR with diminished TR levels indicates inhibition of cellular transcription. This may be important in explaining the variable responses seen with GC treatment for hair regrowth in patients with AA and gives the clinician possible reasons why steroids may not always be effective in treating this difficult hair disease.