Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect
Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect
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DOI：
10.1111/1523-1747.ep12334249
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发表时间：
1997-02-01
影响因子：
6.5
通讯作者：
Bernard, BA
中科院分区：
文献类型：
--
作者：
Michelet, JF;Commo, S;Bernard, BA
文献数据表明，非甾体类抗炎药 (NSAID)，如吲哚美辛、萘普生、吡罗昔康或布洛芬，可在体内诱导脱发。这些 NSAID 是众所周知的前列腺素内过氧化物合酶-1 (PGHS-1) 细胞保护同工型 (PGHS-1) 和诱导型 (PGHS-2) 的抑制剂。通过免疫组织化学染色，我们发现PGHS-1是存在于正常人毛囊（生长期或退行期）的真皮乳头中的主要亚型，而PGHS-2仅在生长期真皮乳头中微弱且专门地表达，因此，PGHS-1可能是NSAIDs毛发生长抑制作用的主要靶标，因此我们推测PGHS-1的激活可能是米诺地尔发挥作用的机制。 (2,4-二氨基-6-哌啶基嘧啶-3-氧化物) 刺激体内毛发生长。我们在此证明米诺地尔是纯化 PGHS-1 (AC50 = 80 muM) 的有效激活剂，通过耗氧量和 PGE(2) 产生进行测定。BALB/c 3T3 成纤维细胞和培养中的人真皮乳头成纤维细胞的 PGE(2) 产生增加也证明了这种激活。我们的研究结果表明，米诺地尔及其衍生物可能在体内具有细胞保护活性，并且基于这种机制可能会设计出更有效的第二代毛发生长药物。
Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair loss in vivo., These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-l (PGHS-1) and of the inducible form (PGHS-2), By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla, Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs, We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 mu M), as assayed by oxygen consumption and PGE(2) production, This activation was also evidenced by increased PGE(2) production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.