Tchernof André, Mansour Mohamed Fouad, Pelletier Mélissa, Boulet Marie-Michèle, Nadeau Mélanie, Luu-The Van
Institut Universitaire de Cardiologie et Pneumologie de Québec, Québec, Canada; École de Nutrition, Université Laval, Québec, Canada; Endocrinologe et Néphrologie, Centre Hospitalier Universitaire de Québec, Québec, Canada.
Institut Universitaire de Cardiologie et Pneumologie de Québec, Québec, Canada; Endocrinologe et Néphrologie, Centre Hospitalier Universitaire de Québec, Québec, Canada.
J Steroid Biochem Mol Biol. 2015 Mar;147:56-69. doi: 10.1016/j.jsbmb.2014.11.011. Epub 2014 Nov 14.
Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11β-HSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer.
在过去十年中，脂肪组织因其内分泌特性，即分泌多种可能产生局部和/或全身效应的脂肪细胞因子的能力，而越来越为人所知。此外，脂肪组织长期以来一直被认为是类固醇激素转化和作用的重要场所。在此，我们提供了一份关于人类脂肪组织中可能检测到的多种类固醇转化酶、它们的活性及潜在作用的最新综述。除了现已明确的芳香化酶和11β-羟基类固醇脱氢酶（HSD）1型的作用外，在脂肪细胞系、分离的成熟细胞和/或前脂肪细胞中还报道了许多酶。这些酶包括11β-HSD 2型、17β-HSDs、3β-HSD、5α-还原酶、硫酸酯酶和葡萄糖醛酸转移酶。其中一些酶被认为与脂肪组织生理学相关，可能也与肥胖的病理生理学有关。脂肪组织细胞类型中这一复杂的类固醇转化酶组值得进一步的科学关注。我们对20α-HSD（AKR1C1）、3α-HSD 3型（AKR1C2）和17β-HSD 5型（AKR1C3）的研究使我们能够阐明这些酶在脂肪组织功能某些方面的相关性。例如，在前脂肪细胞中下调AKR1C2的表达似乎会增强双氢睾酮对该模型中脂肪生成的抑制作用。需要进行许多额外的研究来评估脂肪内类固醇激素转化对脂肪组织功能以及肥胖、糖尿病和癌症等慢性疾病的影响。
