Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus

OBJECTIVE: To determine whether repeated hypoxic insults with umbilical cor d occlusion over 4 days will lead to activation of the hypothalamic-pituita ry-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed ev ery 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization. RESULTS: During umbilical cord occlusions fetal arterial oxygen pressure (a pproximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dio xide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions f or any of the 4 study days. Plasma ACTH increased, as measured after cord o cclusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P < .05). Plasma cortisol increased, as measured after cord occlusio n and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4.7 +/- 0.3 ng/mL, P < .05). POMC mRNA increased 2.5-fold in the par s distalis of the pituitaries from cord occlusion compared to control fetus es, but was unchanged in the pars intermedia. GR mRNA, which was detected i n the pars distalis only, was unaltered. CONCLUSION: Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical r esponsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but w ith no change in GR. (J Soc Gynecol Investig 2000;7;224-32) Copyright (C) 2 000 by the Society for Gynecologic Investigation.