AR polymorphism with shortened CAG repeats (<20) encoding the polyglutamine tract of the N-terminal TAD domain of the AR has been associated with increased genetic disposition for acne and other androgen-driven diseases like hirsutism and androgenetic alopecia.

It is conceivable that a shorter polyglutamine tract of the AR (CAG repeats <20) decreases the ability and affinity for FoxO1 binding, thus increasing coactivator binding and raising the basal state of AR transcriptional activity.

Indirect evidence will be provided in this paper which strongly suggests that acne may be explained by a growth factor-induced nuclear deficiency of FoxO1, whereas isotretinoin increases nuclear FoxO1 levels and thus reverses acne-related imbalances of FoxO homeostasis.

At least four mechanisms of isotretinoin treatment may explain reduced AR transcriptional activity affecting both the FoxO1 regulated N-terminal TAD and the androgen-regulated C-terminal AR ligand binding domain.