Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York, USA.
Division of Endocrinology, Diabetes and Metabolism, Saint Louis University, St. Louis, Missouri, USA.
Diabetes Obes Metab. 2021 Jan;23(1):18-28. doi: 10.1111/dom.14206. Epub 2020 Oct 19.
The role of testosterone in improving sexual symptoms in men with hypogonadism is well known. However, recent studies indicate that testosterone plays an important role in several metabolic functions in males. Multiple PubMed searches were conducted with the use of the terms testosterone, insulin sensitivity, obesity, type 2 diabetes, anaemia, bone density, osteoporosis, fat mass, lean mass and body composition. This narrative review is focused on detailing the mechanisms that underlie the metabolic aspects of testosterone therapy in humans. Testosterone enhances insulin sensitivity in obese men with hypogonadism by decreasing fat mass, increasing lean mass, decreasing free fatty acids and suppressing inflammation. At a cellular level, testosterone increases the expression of insulin receptor β subunit, insulin receptor substrate-1, protein kinase B and glucose transporter type 4 in adipose tissue and adenosine 5'-monophosphate-activated protein kinase expression and activity in skeletal muscle. Observational studies show that long-term therapy with testosterone prevents progression from prediabetes to diabetes and improves HbA1c. Testosterone increases skeletal muscle satellite cell activator, fibroblast growth factor-2 and decreases expression of the muscle growth suppressors, myostatin and myogenic regulatory factor 4. Testosterone increases haematocrit by suppressing hepcidin and increasing expression of ferroportin along with that of transferrin receptor and plasma transferrin concentrations. Testosterone also increases serum osteocalcin concentrations, which may account for its anabolic actions on bone. In conclusion, testosterone exerts a series of potent metabolic effects, which include insulin sensitization, maintenance and growth of the skeletal muscle, suppression of adipose tissue growth and maintenance of erythropoiesis and haematocrit.
睾酮在改善性腺功能减退症男性的性功能障碍症状方面的作用是众所周知的。然而，最近的研究表明，睾酮在男性的几种代谢功能中起着重要作用。使用术语“睾酮”、“胰岛素敏感性”、“肥胖”、“2 型糖尿病”、“贫血”、“骨密度”、“骨质疏松症”、“脂肪量”、“瘦体重”和“身体成分”进行了多次 PubMed 搜索。本综述重点详细阐述了睾酮治疗对人类代谢方面的作用机制。睾酮通过减少脂肪量、增加瘦体重、减少游离脂肪酸和抑制炎症来提高肥胖性腺功能减退症男性的胰岛素敏感性。在细胞水平上，睾酮增加脂肪组织中胰岛素受体β亚基、胰岛素受体底物-1、蛋白激酶 B 和葡萄糖转运蛋白 4 的表达以及骨骼肌中腺苷 5'-单磷酸激活蛋白激酶的表达和活性。观察性研究表明，长期使用睾酮治疗可预防从糖尿病前期进展为糖尿病，并改善 HbA1c。睾酮增加骨骼肌卫星细胞激活物、成纤维细胞生长因子-2，并降低肌肉生长抑制剂肌抑素和肌肉生成调节因子 4 的表达。睾酮通过抑制铁调素和增加铁蛋白的表达以及转铁蛋白受体和血浆转铁蛋白浓度来增加血细胞比容。睾酮还增加血清骨钙素浓度，这可能与其对骨骼的合成代谢作用有关。总之，睾酮发挥了一系列强大的代谢作用，包括胰岛素增敏、维持和生长骨骼肌、抑制脂肪组织生长以及维持红细胞生成和血细胞比容。
