Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes

Elevated levels of prostaglandin D2 (PGD2) have been shown to be present in the bald scalp of androgenic alopecia (AGA) patients and to functionally inhibit hair growth. However, its precise mechanism in AGA has yet to be clearly defined. Although testosterone plays a critical role in the initiation and progression of AGA, the existence of a possible link between PGD2 and testosterone in skin has not been investigated. Here we show that human keratinocytes treated with PGD2 show enhanced capacity to convert the weak androgen, androstenedione, to testosterone. At the same time, treatment with PGD2 induced reactive oxygen species as indicated by generation of the lipid peroxidation product, 4-hydroxynonenal. To determine whether these two events are linked, we used the reactive oxygen species scavenger N-acetyl-cysteine, which blocked the enhanced testosterone production from PGD2-treated keratinocytes. Our study suggests the existence of a possible crosstalk between the PGD2-reactive oxygen species axis and testosterone metabolism in keratinocytes. Thus, we propose that AGA patients might benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging AGA therapies such as finasteride, minoxidil, and PGD2 receptor blockers.