Division of Endocrinology and Metabolism Clinical Chemistry Laboratory, University and Azienda Integrata Ospedaliera Universitaria di Verona, P.le Stefani 1, 37126 Verona, Italy.
Eur J Endocrinol. 2011 Feb;164(2):197-203. doi: 10.1530/EJE-10-0782. Epub 2010 Nov 8.
In hyperandrogenic women, hyperinsulinaemia amplifies 17 α-hydroxycorticosteroid intermediate response to ACTH, without alterations in serum cortisol or androgen response to stimulation. The aim of the study is to assess whether acute hyperinsulinaemia determines absolute changes in either basal or ACTH-stimulated adrenal steroidogenesis in these subjects.
Twelve young hyperandrogenic women were submitted in two separate days to an 8 h hyperinsulinaemic (80 mU/m² × min) euglycaemic clamp, and to an 8 h saline infusion. In the second half of both the protocols, a 4 h ACTH infusion (62.5 μg/h) was carried out. Serum cortisol, progesterone, 17 α-hydroxyprogesterone (17-OHP), 17 α-hydroxypregnenolone (17-OHPREG), DHEA and androstenedione were measured at basal level and during the protocols. Absolute adrenal hormone secretion was quantified by measuring C19 and C21 steroid metabolites in urine collected after the first 4 h of insulin or saline infusion, and subsequently after 4 h of concurrent ACTH infusion.
During insulin infusion, ACTH-stimulated 17-OHPREG and 17-OHP were significantly higher than during saline infusion. No significant differences in cortisol and androgens response to ACTH were found between the protocols. Nevertheless, urinary excretion of ACTH-stimulated C19 and C21 steroid metabolites was significantly higher during hyperinsulinaemia than at basal insulin levels (both P < 0.005). Changes in steroid metabolites molar ratios suggested stimulation by insulin of 5 α-reductase activity.
These in vivo data support the hypothesis that insulin acutely enhances ACTH effects on both the androgen and glucocorticoid pathways.
在高雄激素血症女性中，高胰岛素血症放大了 ACTH 对 17α-羟皮质甾酮中间产物的反应，而对血清皮质醇或雄激素对刺激的反应没有改变。本研究的目的是评估急性高胰岛素血症是否会导致这些患者的基础或 ACTH 刺激肾上腺类固醇生成的绝对变化。
12 名年轻高雄激素血症女性在两天内分别接受 8 小时高胰岛素（80mU/m²×min）和正常血糖钳夹，以及 8 小时盐水输注。在两个方案的后半部分，进行 4 小时 ACTH 输注（62.5μg/h）。在基础水平和方案期间测量血清皮质醇、孕酮、17α-羟孕酮（17-OHP）、17α-羟孕烯醇酮（17-OHPREG）、DHEA 和雄烯二酮。通过测量胰岛素或盐水输注后前 4 小时收集的尿液中的 C19 和 C21 类固醇代谢物，以及随后 4 小时同时进行 ACTH 输注，来定量测定绝对肾上腺激素分泌。
在胰岛素输注期间，ACTH 刺激的 17-OHPREG 和 17-OHP 明显高于盐水输注期间。在两个方案之间，没有发现皮质醇和雄激素对 ACTH 反应的差异。然而，在高胰岛素血症期间，ACTH 刺激的 C19 和 C21 类固醇代谢物的尿排泄明显高于基础胰岛素水平（均 P<0.005）。类固醇代谢物摩尔比的变化表明胰岛素急性刺激 5α-还原酶活性。
这些体内数据支持了胰岛素急性增强 ACTH 对雄激素和糖皮质激素途径的作用的假说。
