prostaglandin-d2 and Alopecia

Androgenetic alopecia is the progressive miniaturization of the scalp's terminal follicles in aging men. Over 40% of Caucasian men develop hair loss by the age of 40. Despite its prevalence, there are only two FDA approved medications to treat the condition. Recognizing the unmet need, new medical, procedural, and surgical treatments are being adopted to combat progressive hair loss. This review examines emerging hair loss treatments including medical therapies that the target prostaglandins, low level light therapy, platelet rich plasma injections, and robotic hair transplantation.

Topics: Alopecia; Dinoprost; Hair Follicle; Humans; Low-Level Light Therapy; Male; Platelet-Rich Plasma; Prostaglandin D2; Prostaglandins; Robotic Surgical Procedures

Lipids in the skin are the most diverse in the entire human body. Their bioactivity in health and disease is underexplored. Prostaglandin D2 has recently been identified as a factor which is elevated in the bald scalp of men with androgenetic alopecia (AGA) and has the capacity to decrease hair lengthening. An enzyme which synthesizes it, prostaglandin D2 synthase (PTGDS or lipocalin-PGDS), is hormone responsive in multiple other organs. PGD2 has two known receptors, GPR44 and PTGDR. GPR44 was found to be necessary for the decrease in hair growth by PGD2 . This creates an exciting opportunity to perhaps create novel treatments for AGA, which inhibit the activity of PTGDS, PGD2 or GPR44. This review discusses the current knowledge surrounding PGD2 , and future steps needed to translate these findings into novel therapies for patients with AGA.

Topics: Alopecia; Animals; Humans; Intramolecular Oxidoreductases; Lipocalins; Male; Prostaglandin D2

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.

Topics: Acetylcysteine; Aldehydes; Alopecia; Androstenedione; Cells, Cultured; Free Radical Scavengers; Humans; Keratinocytes; Prostaglandin D2; Reactive Oxygen Species; Signal Transduction; Testosterone

Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

Topics: Alopecia; Apoptosis; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Hair; Hair Follicle; Humans; Keratinocytes; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin

Androgenic alopecia, a condition characterized by increased levels of DHT could have been selected for due to the benefits that prostaglandin D2 (PGD(2)) has on the prostate. A DHT metabolite can increase the transcription of prostaglandin D2 synthase through estrogen receptor beta. The increase of PGD(2) can decrease the risk of prostate cancer and proliferation of prostate cancer cells. Therefore, the mechanisms behind male pattern baldness may also curtail the advancement of prostate cancer.

Topics: Adult; Alopecia; Androgens; Cell Proliferation; Dihydrotestosterone; Finasteride; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Models, Theoretical; Prostaglandin D2; Prostatic Neoplasms

Topics: Alopecia; Humans; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin

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 D(2) 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 D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) 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 PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.

Topics: Alopecia; Animals; Epidermis; Female; Gene Expression Profiling; Hair; Hair Follicle; Humans; Keratinocytes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Receptors, Immunologic; Receptors, Prostaglandin; Scalp