Testosterone metabolism to 5α-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes
Testosterone metabolism to 5α-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes
复制标题
DOI：
10.1111/j.1365-2133.2006.07671.x
复制
发表时间：
2007-03-01
影响因子：
10.3
通讯作者：
Zouboulis, C. C.
中科院分区：
文献类型：
--
作者：
Makrantonaki, E.;Zouboulis, C. C.
尽管临床证据表明雄激素刺激皮脂腺脂质，但体外实验显示雄激素没有类似的作用。这一矛盾导致了脂质调节可能需要辅因子的假设，过氧化物酶体增殖激活受体（PPAR）配体被认为是适当的候选者。目的观察睾酮和PPAR配体亚油酸单独或联合5 α -还原酶I型抑制剂LY191704对人SZ95皮脂细胞5 α -二氢睾酮（5 α - dht）合成及脂质含量的影响。方法采用4- methylumbellliferyl heptanoate荧光法和Boehringer Lactate Dehydrogenase assay kit检测细胞增殖和活力。5 - dht酶联免疫吸附法检测处理后细胞上清液中5 - dht的合成，而脂质生成则通过尼罗红脂质微测定法和荧光显微镜记录。结果睾酮促进5 - dht合成（P < 0.001），而亚油酸增加皮脂腺脂质（P < 0.001）。睾酮和亚油酸联合使用对5 α - dht合成（P < 0.01）和皮脂脂质的合成（P < 0.01）有协同作用（P < 0.01）。与睾酮/亚油酸相比，LY191704可显著降低5 - dht和皮脂水平（P < 0.01和P < 0.001）。细胞增殖和活力在所有化合物处理下保持不变。结论PPAR配体通过5 α还原对细胞睾酮活化具有催化作用，而5 α还原对皮脂脂质的调节具有重要意义。
Background Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator-activated receptor (PPAR) ligands were suggested to be adequate candidates.Objectives The influence of testosterone and linoleic acid, a PPAR ligand, as single agents and in combination with of LY191704, a 5 alpha-reductase type I inhibitor, was examined on 5 alpha-dihydrotestosterone (5 alpha-DHT) synthesis and lipid content in human SZ95 sebocytes.Methods Cell proliferation and viability were measured by the 4-methylumbelliferyl heptanoate fluorescence assay and by the Boehringer Lactate Dehydrogenase Assay kit, respectively. 5 alpha-DHT enzyme-linked immunosorbent assay was used for the detection of 5 alpha-DHT synthesis in cell supernatants after treatment, whereas lipid production was documented by means of the Nile red lipid microassay and fluorescence microscopy.Results Testosterone promoted 5 alpha-DHT synthesis (P < 0.001), whereas linoleic acid increased sebaceous lipids (P < 0.001). The combination of testosterone and linoleic acid exhibited a synergistic effect on the synthesis of 5 alpha-DHT (P < 0.01 vs. testosterone) and sebaceous lipids (P < 0.01 vs. linoleic acid). Furthermore, LY191704 reduced 5 alpha-DHT and sebaceous lipid levels (P < 0.01 and P < 0.001 in comparison with testosterone/linoleic acid, respectively). Cell proliferation and viability remained unchanged under treatment with all compounds tested.Conclusions These data suggest a catalytic effect of PPAR ligands on cellular testosterone activation by 5 alpha-reduction and the importance of the latter for the regulation of sebaceous lipids.