This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Green, L. R. Articles by Richardson, B. S. Search for Related Content PubMed PubMed Citation Articles by Green, L. R. Articles by Kawagoe, Y. Articles by Fraser, M. Articles by Challis, J. R. G. Articles by Richardson, B. S. Social Bookmarking                         What's this?

Activation of the Hypothalamic-Pituitary-Adrenal Axis With Repetitive Umbilical Cord Occlusion in the Preterm Ovine Fetus

MRC Group in Fetal and Neonatal Health and Development, Departments of Obstetrics and Gynecology and Physiology, The Lawson Research Institute, The University of Western Ontario, London, Ontario, Canada; and Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Centre for Fetal Origins of Adult Disease, 887(F) Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, US; lucygreen{at}hotmail.com

Y. Kawagoe, MD

M. Fraser, PhD

J. R. G. Challis, PhD, DSc

B. S. Richardson, MD

MRC Group in Fetal and Neonatal Health and Development, Departments of Obstetrics and Gynecology and Physiology, The Lawson Research Institute, The University of Western Ontario, London, Ontario, Canada; and Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Objective: To determine whether repeated hypoxic insults with umbiblical 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: Umbiblical 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, palsma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization.

Results: During umbiblical 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.

Conclusion: Repetitive unbiblical 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 ditalis and pars intermedia of the pituitary, but with no change in GR.

Key Words: Umbilical cord occlusion • ovine • fetus • ACTH • cortisol

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 4, 224-232 (2000)
DOI: 10.1177/107155760000700406


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?