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 cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus.


METHODS
Umbilical cord occlusions of 90 seconds duration were performed every 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 (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion 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 occlusion 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 pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered.


CONCLUSIONS
Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.
Green
L R
LR
Department of Obstetrics and Gynecology, London, Ontario, Canada. lucygreen@hotmail.com
Kawagoe
Y
Y
Fraser
M
M
Challis
J R
JR
Richardson
B S
BS
D000311:Adrenal Glands / Q000196:embryology* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001158:Arteries; D003250:Constriction; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D007031:Hypothalamus / Q000196:embryology* / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010902:Pituitary Gland / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012756:Sheep; D014470:Umbilical Cord / Q000502:physiology*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D010100:Oxygen; D006854:Hydrocortisone