Acta Demato-Venereologica 98-3CompleteContent

318 REVIEW ARTICLE Prostanoids and Hair Follicles: Implications for Therapy of Hair Disorders Xue-Gang XU and Hong-Duo CHEN Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China Prostanoids, including prostaglandins (PGs) and throm- boxane A 2 (TXA 2 ), are a family of lipid-derived auta- coids that modulate many physiological systems and pathological contexts. Prostanoids are generated by sequential metabolism of arachidonic acid, catalysed by cyclo-oxygenase, to PGH2, which is then conver- ted to PGD 2 , PGE 2 , PGF 2α , PGI 2 and TXA 2 , catalysed by their specific synthases. Recent evidence suggests that prostanoids play a role in regulating hair growth. The PGF 2α analogue is Food and Drug Administration- approved in the US and routinely used to enhance the growth of human eyelashes. PGE 2 is reported to pro- tect from radiation-induced hair loss in mice. Conver- sely, PGD 2 inhibits hair growth. This paper reviews the metabolism of prostanoids and the expression pattern of prostanoid receptors in hair follicles, focussing on their different and opposing effects on hair growth and the underlying mechanisms. This has potential clinical relevance in the treatment and prevention of hair dis orders. PROSTANOID METABOLISM There are 2 main COX isoforms, COX-1 and COX-2, both of which can transform arachidonic acid into PGH2. COX-1 is constitutively expressed, while COX-2 is indu- ced by mitogenic and pro-inflammatory stimuli. PGH 2 is then transformed into different PGs and TXA 2 , catalysed by different synthases. The mainly bioactive prostanoids generated in vivo include PGE 2 , PGI 2 , PGD 2 , PGF 2α , and TXA 2 . TXA 2 is characterized as modulating haemodyna- mics and cardiovascular functions; therefore this review focusses on other PGs. Prostanoids act as autocrine/ paracrine local hormones through specific G-protein- coupled receptors. The 5 types of prostanoids, PGE 2 , PGI 2 , PGD 2 , PGF 2α , and TXA 2 , bind to PGE 2 receptors (EP 1 , EP 2 , EP 3 , EP 4 ), PGI 2 receptor (IP), PGD 2 receptors (DP 1 , DP 2 ), PGF 2α receptor (FP), and thromboxane A 2 receptor (TP) respectively (Fig. 1). Different prostanoids have different, or even opposing, properties, possibly due to the fact that they bind to different receptors and Key words: prostanoid; prostaglandin r eceptor; PGF2α analo- gue; hair follicle. Accepted Nov 13, 2017; Epub ahead of print Nov 14, 2017 Acta Derm Venereol 2018; 98: 318–323. Corr: Hong-Duo Chen, Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang 110001 China. E-mail: hongduochen@ hotmail.com P rostaglandins (PGs) and thromboxane A 2 (TXA 2 ) are termed prostanoids and are derived from arachidonic acid and other long-chain polyunsaturated fatty acids (1). The biosynthesis of prostanoids begins with the release of arachidonic acid from the plasma membrane of cells by phospholipases (PLAs), following metabolism via the sequential actions of cyclo-oxygenase (COX) and respec- tive synthases. Prostanoids modulate many physiological systems, including the immune, respiratory, gastrointesti- nal, cardiovascular, and genitourinary systems (1, 2). Research on prostanoids has focused on inflammation and inflammatory responses, and the relationship bet- ween prostanoids and hair follicles has been investigated largely through adverse events and case reports (3, 4). This review discusses the biosynthesis of prostanoids and their metabolism in hair follicles, with particular regard to advances in research into prostanoids and hair follicle growth, hair follicle cycle, and hair disorders. doi: 10.2340/00015555-2843 Acta Derm Venereol 2018; 98: 318–323 Fig. 1. Schematic of the biosynthesis of prostanoids and their biological effects on hair follicles via activating different cell surface G protein-coupled receptors. Different prostanoids can bind different receptors and G-protein, trigger different second messengers and lead to different effects to hair follicles. PDF 2α analogues can activate FP. DP2 antagonists can inhibit DP2 activation. All have treatment potential for hair loss. COX1: cyclo-oxygenase 1; COX2: cyclo-oxygenase 2; PGG 2 : prostaglandin G 2 ; PGH 2 : prostaglandin H 2 ; TxAS: TXA 2 synthase; PGDS: PGD 2 synthase; PGES: PGE 2 synthase; PGFS: PGF 2α synthase; PGIS: PGI 2 synthase; TXA 2 : thromboxane A 2 ; PGD 2 : prostaglandin D 2 ; PGE 2 : prostaglandin E 2 ; PGF 2α : prostaglandin F 2α ; PGI 2 : prostaglandin I 2 ; TP: TXA 2 receptor; DP1: PGD 2 receptor 1; DP 2 : PGD 2 receptor 2; EP: PGE 2 receptor; FP: PGF 2α receptor; IP: PGI 2 receptor. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.

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