Prostaglandin D ₂ Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

Abstract

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein (heterotrimeric guanine nucleotide)–coupled receptor 44 (GPR44), but not the PGD2 receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.

Androgenetic Alopecia: A Chronic or Pubertal Onset Disease Retarded by Blood Donation

“…Another factor suggested to mediate hair fall is an increased autoimmune reaction against hair follicles [41]. This hypothetical mechanism was confirmed by a significant increase in WBC count and lymphocyte percent in contrast to other WBC cells (Table 2).…”

Structural and dynamic insights into substrate binding and catalysis of human lipocalin prostaglandin D synthase

“…In addition, studies by various research groups have proposed the diagnostic application of L-PGDS in obstructive azoospermia ( 17 ), and neurological disorders ( 18 ). Recently L-PGDS and PGD 2 were linked to hair loss and were found to be overexpressed on the bald scalp of patients suffering from androgenetic alopecia ( 19 ).…”

Hair growth promoting effects of emodin in telogenic C57BL/6 mice

“…Five alpha-reductase, which is produced in many tissues of males and females, participates in steroid metabolism that leads to conversion of testosterone into DHT [3,7,21]. PGD2 also inhibits hair growth of patients with androgenetic alopecia and has the capacity to decrease hair lengthening [5,11]. Emodin possesses antioxidative activities including increased superoxide dismutase (SOD) activity, and SOD1, SOD2, and cytosolic glutathione peroxidase mRNA as well as anti-inflammatory activities.…”

“…Because DHT shortens the growth phase of the follicles and size of the hair follicles, it is considered to be a potent agent at triggering hair growth and/or hair loss [7,8,21]. Recent studies have reported that prostaglandin D2 (PGD2) was abnormally more abundant in a bald scalp than a haired scalp, especially for patients with androgenetic alopecia, and that it had the capacity to decrease hair lengthening [5,11].…”