Chang Y T, Ghirri P, Migeon C J, Brown T R
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Androl. 1992 May-Jun;13(3):242-8.
Previous reports have suggested a relationship between hyperinsulinemia and increased androgen secretion leading to female virilization, but no report has been made of the effects of insulin on androgen receptors. The authors tested the in vitro effect of insulin on the binding of methyltrienolone (R1881) to androgen receptors of cultured genital skin fibroblasts preincubated with serum-free medium in the absence and presence of insulin (100 ng/mL, ie, 2600 microU/mL) for 18 hours at 37 degrees C. Insulin increased specific binding of R1881 by 35% (range, 13% to 75%). Scatchard analysis of androgen receptor binding demonstrated a similar increase in the number of binding sites, whereas binding affinity remained unchanged. The increase in androgen receptors was dose dependent (maximum effect at 25 ng insulin/mL) and time dependent (maximum effect occurring after 12 hours). DNA measurements indicated that insulin increased binding sites per cell rather than altering the cell number. Insulin increased total protein concentration to an extent similar to that observed for the increase in androgen receptor binding sites. Cycloheximide, but no actinomycin D, inhibited the effect of insulin on androgen receptor binding. The authors' data suggest that insulin induces an increase in the number of androgen receptors per cell as part of a general anabolic effect on cellular protein content.
以往的报告表明，高胰岛素血症与雄激素分泌增加导致女性男性化之间存在关联，但尚未有关于胰岛素对雄激素受体影响的报道。作者测试了胰岛素在体外对甲基三烯醇酮（R1881）与培养的生殖器皮肤成纤维细胞雄激素受体结合的影响，这些细胞在无血清培养基中预孵育，分别在有无胰岛素（100 ng/mL，即2600 μU/mL）的情况下于37℃孵育18小时。胰岛素使R1881的特异性结合增加了35%（范围为13%至75%）。对雄激素受体结合的Scatchard分析表明，结合位点数量有类似增加，而结合亲和力保持不变。雄激素受体的增加呈剂量依赖性（胰岛素浓度为25 ng/mL时达到最大效应）和时间依赖性（12小时后达到最大效应）。DNA测量表明，胰岛素增加了每个细胞的结合位点，而不是改变细胞数量。胰岛素使总蛋白浓度增加的程度与雄激素受体结合位点增加的程度相似。放线菌酮可抑制胰岛素对雄激素受体结合的作用，而放线菌素D则无此作用。作者的数据表明，胰岛素诱导每个细胞的雄激素受体数量增加，这是对细胞蛋白质含量的一种普遍合成代谢作用的一部分。
