Tommy's Centre for Maternal and Fetal Health, Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
Clin Endocrinol (Oxf). 2018 Apr;88(4):592-600. doi: 10.1111/cen.13548. Epub 2018 Jan 29.
Hypothalamic-pituitary-adrenal axis (HPA) activity is decreased in obese pregnancy and associates with increased foetal size. Pulsatile release of glucocorticoid hormones regulates their action in target tissues. Glucocorticoids are essential for normal foetal growth, but little is known about glucocorticoid pulsatility in pregnancy. We aimed to investigate the ultradian rhythm of glucocorticoid secretion during obese and lean pregnancy and nonpregnancy.
Serum cortisol, cortisone, corticosterone and 11-dehydrocorticosterone were measured by LC-MS/MS from samples obtained at 10-minute intervals between 08.00-11.00 hours and 16.00-19.00 hours, from 8 lean (BMI <25 kg/m ) and 7 obese (BMI > 35 kg/m ) pregnant women between 16-24 weeks gestation and again at 30-36 weeks), and nonpregnant controls (lean n = 3, obese n = 4) during the luteal phase of their menstrual cycle. Interstitial fluid cortisol was measured by ELISA, from samples obtained using a portable microdialysis and automated collection device at 20-minute intervals over 24 hours.
Serum cortisol AUC, highest peak and lowest trough increased significantly with gestation in lean and obese pregnant compared with nonpregnant subjects. Pulsatility of cortisol was detected in interstitial fluid. In pregnant subjects, interstitial fluid pulse frequency was significantly lower with advancing gestation in obese, but not in lean.
We demonstrate cortisol pulsatility in interstitial fluid. Pulse frequency is altered with increased gestation and BMI. This may be a novel mechanism to explain decreased HPA activity in obese pregnancy.
肥胖妊娠时下丘脑-垂体-肾上腺轴（HPA）活性降低，与胎儿大小增加有关。糖皮质激素激素的脉冲释放调节其在靶组织中的作用。糖皮质激素对于正常胎儿生长是必不可少的，但对于妊娠期间糖皮质激素的脉冲性知之甚少。我们旨在研究肥胖和瘦素妊娠和非妊娠期间糖皮质激素分泌的超昼夜节律。
通过 LC-MS/MS 从 8 名 16-24 周妊娠的瘦素（BMI<25 kg/m ）和 7 名肥胖（BMI>35 kg/m ）孕妇以及再次在 30-36 周时和 8 名非妊娠对照组（瘦素 n=3，肥胖 n=4）在月经周期的黄体期，每 10 分钟采集一次 08.00-11.00 小时和 16.00-19.00 小时的血清样本，测量皮质醇、可的松、皮质酮和 11-脱氢皮质酮。使用便携式微透析和自动采集装置，以 20 分钟的间隔在 24 小时内采集间质液皮质醇样本，通过 ELISA 进行测量。
与非妊娠对照组相比，瘦素和肥胖孕妇的血清皮质醇 AUC、最高峰值和最低谷值随妊娠显著增加。间质液中检测到皮质醇的脉冲性。在孕妇中，随着妊娠的进展，肥胖孕妇间质液脉冲频率显著降低，但瘦素孕妇则没有。
我们证明了间质液中皮质醇的脉冲性。随着妊娠和 BMI 的增加，脉冲频率发生改变。这可能是解释肥胖妊娠时 HPA 活性降低的一种新机制。
