Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey.
Department of Medical Biochemistry, Ankara University Medical Faculty, Ankara, Turkey.
Horm Metab Res. 2020 Sep;52(9):654-659. doi: 10.1055/a-1116-2173. Epub 2020 Feb 27.
Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients.
雄激素在肾脏、心脏、肝脏和胰腺等非生殖器官中发挥着关键作用。由于雄激素受体在胰腺和肝细胞中表达，过多的睾酮可导致胰岛素和胎球蛋白-A（一种在肝脏中产生的蛋白质）过度分泌。胎球蛋白-A 的表达是一种天然的肌肉和肝脏酪氨酸激酶活性抑制剂，可导致胰岛素抵抗。此外，胰岛素和胎球蛋白-A 水平被认为受药物如糖皮质激素（GCs）和氟氢可的松的影响。然而，经典先天性肾上腺增生症（CAH）患者的雄激素和 GCs 是否会影响胎球蛋白-A 和胰岛素水平尚不清楚。这项横断面研究纳入了 56 名 CAH 患者和 70 名对照。为了控制与性激素产生相关的血清代谢/炎症标志物的潜在变化，按性别和青春期前/青春期状态进行了分析。在血液样本中测量了空腹血糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、天冬氨酸转氨酶、丙氨酸转氨酶、胎球蛋白-A 和高敏 C 反应蛋白（hs-CRP）水平。此外，在给药前测量了 17α-羟孕酮、雄烯二酮、总睾酮、游离睾酮和硫酸脱氢表雄酮水平。CAH 患者的胰岛素和胎球蛋白-A 水平明显高于对照组。这些物质的不利高水平与总睾酮和游离睾酮呈正相关。回归分析显示，胎球蛋白-A 和游离睾酮是胰岛素水平的唯一独立预测因子，而胰岛素和游离睾酮水平显著预测了胎球蛋白-A 水平（分别为 R42.7%和 59.8%）。青春期和青春期前组之间的甘油三酯和 hs-CRP 水平也存在差异。我们得出结论，血清胎球蛋白-A 和胰岛素水平可能与 CAH 患者的雄激素有关。
