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

Abstract

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.

Systemic dexpanthenol as a novel treatment for female pattern hair loss

“…It is well established that certain prostaglandins (PG) such as PGD2, which may be released after reactive oxygen species induced tissue damage, may have a crucial role in the pathogenesis of androgenetic alopecia by increasing testosterone. This pathway may be one of the possible effects of DXP on androgenetic alopecia 22‐24 . Of note, a previous animal study reported that bristles of the female swine suffering from a deficiency of pantothenic acid loosen and fall, in particular on the rump and along the spine 25 .…”

Prostaglandins in androgenetic alopecia in 12 men and four female

“…PGD2 activity is mediated by the PGD2 receptor PTGDR2 (GPR44). 1,2 A Mantel et al 3 suggested that reactive oxygen species (ROS)-driven function in hair follicles keratinocytes is the molecular mechanism by which PGD2 induced testosterone synthesis. Induction of ROS by PGD2 is attributed to 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), a spontaneous electrophilic metabolite of PGD2.…”

“…Villarreal-Villarreal, 1,2 R.D. Sinclair, 3,4 L. Mart ınez-Jacobo, 2,5,6 V. Garza-Rodr ıguez, 1 S.A. Rodr ıguez-Le on, 1 A.C. Lamadrid-Zertuche, 2 R. Rodr ıguez-Gutierrez, 7 R. Ortiz-Lopez, 2,8 A. Rojas-Martinez, 2,8 J. Ocampo-Candiani 1, *…”

Dermatology today and tomorrow: from symptom control to targeted therapy

“…More recently, it has become apparent that prostaglandins, specifically PGD2, can also inhibit hair growth . PGD2 appears to act by enhancing testosterone formation through crosstalk between the PGD2‐reactive oxygen species (ROS) axis and testosterone metabolism in keratinocytes, suggesting that AGA patients might benefit from the use of an ROS scavenger like N‐acetyl‐cysteine or other antioxidants in addition to other AGA therapies …”