Pulsatility of Glucocorticoid Hormones in Pregnancy: Changes with Gestation and Obesity

Abstract

Objective

Hypothalamic-pituitary-adrenal-axis (HPA) activity is decreased in obese pregnancy and associates with increased fetal size. Pulsatile release of glucocorticoid hormones regulates their action in target tissues. Glucocorticoids are essential for normal fetal 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 non-pregnancy.

Design

Serum cortisol, cortisone, corticosterone and 11-dehydrocorticosterone were measured by LC-MS/MS from samples obtained at 10-minute intervals between 08.00-11.00h and 16.00h-19.00h, from eight lean (BMI <25kg/m2) and seven obese (BMI >35kg/m2) pregnant women between 16-24 weeks gestation and again at 30-36 weeks), and non-pregnant 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.

Results

Serum cortisol AUC, highest peak, and lowest trough increased significantly with gestation in lean and obese pregnant compared with non-pregnant 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.

Conclusions

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.

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