O'Reilly Michael W, House Philip J, Tomlinson Jeremy W
Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
J Steroid Biochem Mol Biol. 2014 Sep;143:277-84. doi: 10.1016/j.jsbmb.2014.04.008. Epub 2014 Apr 28.
Androgens play an important role in regulation of body fat distribution in humans. They exert direct effects on adipocyte differentiation in a depot-specific manner, via the androgen receptor (AR), leading to modulation of adipocyte size and fat compartment expansion. Androgens also impact directly on key adipocyte functions including insulin signalling, lipid metabolism, fatty acid uptake and adipokine production. Androgen excess and deficiency have implications for metabolic health in both males and females, and these metabolic effects may be mediated through adipose tissue via effects on fat distribution, adipocyte function and lipolysis. Research into the field of androgen metabolism in human and animal adipose tissue has produced inconsistent results; it is important to take into account the sex-, depot- and organism-specific effects of androgens in fat. In general, studies point towards a stimulatory effect on lipolysis, with impairment of adipocyte differentiation, insulin signalling and adipokine generation. Observed effects are frequently gender-specific. Adipose tissue is an important organ of pre-receptor androgen metabolism, through which local androgen availability is rigorously controlled. Adipose androgen exposure is tightly controlled by isoenzymes of AKR1C, 5α-reductase and others, but regulation of the balance between generation and irreversible inactivation remains poorly understood. In particular, AKR1C2 and AKR1C3 are crucial in the regulation of local androgen bioavailability within adipose tissue. These isoforms control the balance between activation of androstenedione (A) to testosterone (T) by the 17β-hydroxysteroid dehydrogenase activity (17β-HSD) of AKR1C3, or inactivation of 5α-dihydrotestosterone (DHT) to 5α-androstane-3α,17β-diol by the 3α-hydroxysteroid dehydrogenase (3α-HSD) activity of AKR1C2. Most studies suggest that androgen inactivation is the predominant reaction in fat, particularly in the abdominal subcutaneous (SC) depot. Modulation of local adipose androgen availability may afford future therapeutic options to improve metabolic phenotype in disorders of androgen excess and deficiency.
雄激素在调节人体脂肪分布中起着重要作用。它们通过雄激素受体（AR）以特定部位的方式对脂肪细胞分化产生直接影响，从而调节脂肪细胞大小和脂肪隔室扩张。雄激素还直接影响关键的脂肪细胞功能，包括胰岛素信号传导、脂质代谢、脂肪酸摄取和脂肪因子产生。雄激素过多和缺乏对男性和女性的代谢健康都有影响，这些代谢效应可能通过对脂肪分布、脂肪细胞功能和脂肪分解的影响，经由脂肪组织介导。对人类和动物脂肪组织中雄激素代谢领域的研究结果并不一致；考虑雄激素在脂肪中的性别、部位和生物体特异性效应很重要。一般来说，研究表明雄激素对脂肪分解有刺激作用，同时损害脂肪细胞分化、胰岛素信号传导和脂肪因子生成。观察到的效应通常具有性别特异性。脂肪组织是受体前雄激素代谢的重要器官，通过它可以严格控制局部雄激素的可用性。脂肪组织中的雄激素暴露受到AKR1C、5α-还原酶等同工酶的严格控制，但对生成与不可逆失活之间平衡的调节仍知之甚少。特别是，AKR1C2和AKR1C3在调节脂肪组织内局部雄激素的生物利用度方面至关重要。这些同工型通过AKR1C3的17β-羟基类固醇脱氢酶活性（17β-HSD）控制雄烯二酮（A）向睾酮（T）的激活平衡，或通过AKR1C2的3α-羟基类固醇脱氢酶（3α-HSD）活性控制5α-二氢睾酮（DHT）向5α-雄烷-3α,17β-二醇的失活平衡。大多数研究表明，雄激素失活是脂肪中的主要反应，尤其是在腹部皮下（SC）脂肪库中。调节局部脂肪组织中雄激素的可用性可能为改善雄激素过多和缺乏症的代谢表型提供未来的治疗选择。
