Endocrine Section, Department of Medicine, Salem Veterans Affairs Medical Center, Salem, Virginia 24153, USA.
Eur J Endocrinol. 2010 Jun;162(6):1043-9. doi: 10.1530/EJE-10-0149. Epub 2010 Mar 18.
While androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, placebo and testosterone, testosterone and dutasteride (to block 5alpha-reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebo-controlled, prospectively randomized design.
Subjects received i.v. injection of saline, GHRH, GH-releasing peptide-2 (GHRP-2), somatostatin (SS), and GHRP-2/GHRH/l-arginine (triple stimulus) each on separate mornings fasting. Outcomes comprised cortisol concentrations, pulsatile cortisol secretion, and relationships with age or abdominal visceral fat (AVF).
By ANCOVA, baseline (saline-infused) cortisol concentrations (nmol/l) did not differ among the sex-steroid milieus (overall mean 364+/-14). In contrast, stimulated peak cortisol concentrations were strongly determined by secretagogue type (P<0.001) as follows: triple stimulus (868+/-27)>GHRP-2 (616+/-42)>saline=SS=GHRH (grand mean 420+/-21). After GHRP-2 injection, pulsatile cortisol secretion increased with age (R(2)=0.16, P=0.012). After the triple stimulus, pulsatile cortisol secretion correlated i) inversely with serum 5alpha-dihydrotestosterone (DHT) concentrations (R(2)=0.53, P=0.026) and ii) directly with computerized tomography-estimated AVF (R(2)=0.11, P=0.038).
Age, DHT concentrations, AVF, and secretagogue type influence pulsatile cortisol secretion at least in men. Further studies should be performed to assess ACTH secretion and native ghrelin action in defined sex-steroid milieus.
虽然雄激素和雌激素在动物模型中控制糖皮质激素的分泌，但性别类固醇环境如何决定人类的皮质醇分泌还不太清楚。为了解决这个问题，我们在一项双盲、安慰剂对照、前瞻性随机设计中，测量了 42 名健康男性在 5 小时内每隔 10 分钟采集的血清中皮质醇的浓度，这些男性分别接受了静脉注射生理盐水、GHRH、生长激素释放肽-2（GHRP-2）、生长抑素（SS）和 GHRP-2/GHRH/L-精氨酸（三重刺激），同时还接受了双安慰剂、安慰剂和睾酮、睾酮和 dutasteride（阻断 5α-还原酶 I 型和 II 型）或睾酮和 anastrozole（阻断芳香酶）治疗。
受测者在禁食的情况下，分别在不同的早晨接受静脉注射生理盐水、GHRH、生长激素释放肽-2（GHRP-2）、生长抑素（SS）和 GHRP-2/GHRH/L-精氨酸（三重刺激）。研究结果包括皮质醇浓度、皮质醇脉冲分泌以及与年龄或腹部内脏脂肪（AVF）的关系。
通过方差分析（ANCOVA），不同性别类固醇环境下的基础（生理盐水输注）皮质醇浓度（nmol/l）没有差异（总体平均值 364+/-14）。相比之下，刺激后的皮质醇峰值浓度强烈取决于激动剂类型（P<0.001），如下所示：三重刺激（868+/-27）>GHRP-2（616+/-42）>生理盐水=SS=GHRH（总平均值 420+/-21）。在 GHRP-2 注射后，皮质醇脉冲分泌随年龄增加而增加（R(2)=0.16，P=0.012）。在三重刺激后，皮质醇脉冲分泌与血清 5α-二氢睾酮（DHT）浓度呈负相关（R(2)=0.53，P=0.026），与计算机断层扫描估计的腹部内脏脂肪（AVF）呈正相关（R(2)=0.11，P=0.038）。
年龄、DHT 浓度、AVF 和激动剂类型至少在男性中影响皮质醇脉冲分泌。应进一步研究以评估在特定性别类固醇环境中 ACTH 分泌和内源性 ghrelin 作用。
