Departments of PathologyDermatologyTohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanBiological Science LaboratoriesKao Corporation, Haga, Tochigi, JapanDepartments of DermatologyVenereology, Allergology and Immunology, Dessau Medical Center, Dessau, GermanyDepartments of PathologyDermatologyTohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanBiological Science LaboratoriesKao Corporation, Haga, Tochigi, JapanDepartments of DermatologyVenereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
Departments of PathologyDermatologyTohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanBiological Science LaboratoriesKao Corporation, Haga, Tochigi, JapanDepartments of DermatologyVenereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
J Endocrinol. 2014 Sep;222(3):301-12. doi: 10.1530/JOE-14-0323. Epub 2014 Jun 17.
Androgens are well known to influence sebum synthesis and secretion. Various factors related to androgen biosynthesis are expressed in human sebaceous glands. In this study, immunohistochemical analysis of human skin specimens from 43 subjects indicated that various androgen-producing and -metabolizing enzymes were functionally localized to sebocytes accumulating lipid droplets and that the exclusive expression of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2 (HSD17B2)) in sebaceous glands was negatively correlated with that of peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), which also significantly changed in an age-dependent manner. We also demonstrated that the changes of 17β-HSD2 expression in human immortalized sebocytes (SZ95) influenced the expressions of sebogenesis-related factors. In addition, the overexpression of 17β-HSD2 in SZ95 significantly increased the androstenedione production and markedly decreased the amounts of testosterone and dihydrotestosterone when DHEA was added externally. On the other hand, the phosphorylation of mammalian target of rapamycin, which is well known to induce sebum secretion and the onset and/or aggravation of acne, was increased by the addition of testosterone in the presence of IGF1 in hamster sebocytes. These results all indicated that local androgen biosynthesis and metabolism in human sebaceous glands could play a pivotal role in sebum synthesis and secretion.
雄激素众所周知会影响皮脂的合成和分泌。与雄激素生物合成有关的各种因素在人类皮脂腺中表达。在这项研究中，对 43 名受试者的皮肤标本进行免疫组织化学分析表明，各种产生和代谢雄激素的酶在堆积脂质滴的皮脂细胞中具有功能性定位，并且 17β-羟类固醇脱氢酶 2（17β-HSD2（HSD17B2））在皮脂腺中的特异性表达与过氧化物酶体增殖物激活受体 γ（PPARγ（PPARG））呈负相关，后者也呈年龄依赖性显著变化。我们还证明，人永生化皮脂细胞（SZ95）中 17β-HSD2 表达的变化影响皮脂生成相关因子的表达。此外，当 DHEA 外源性添加时，SZ95 中 17β-HSD2 的过表达显著增加了雄烯二酮的产生，并显著减少了睾酮和二氢睾酮的量。另一方面，在仓鼠皮脂细胞中存在 IGF1 的情况下，添加睾酮会增加雷帕霉素靶蛋白（mTOR）的磷酸化，mTOR 是众所周知的会诱导皮脂分泌以及痤疮的发生和/或加重。这些结果均表明，人类皮脂腺中的局部雄激素生物合成和代谢可能在皮脂合成和分泌中起关键作用。
