Medical College of Wisconsin
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Programming of the hypothalamic-pituitary-adrenal axis by neonatal intermittent hypoxia: effects on adult male ACTH and corticosterone responses are stress specific. Endocrinology 2014 May;155(5):1763-70



Pubmed ID




Scopus ID

2-s2.0-84899446238   18 Citations


Intermittent hypoxia (IH) is an animal model of apnea-induced hypoxia, a common stressor in the premature neonate. Neonatal stressors may have long-term programming effects in the adult. We hypothesized that neonatal exposure to IH leads to significant changes in basal and stress-induced hypothalamic-pituitary-adrenal (HPA) axis function in the adult male rat. Rat pups were exposed to normoxia (control) or 6 approximately 30-second cycles of IH (5% or 10% inspired O₂) daily on postnatal days 2-6. At approximately 100 days of age, we assessed the diurnal rhythm of plasma corticosterone and stress-induced plasma ACTH and corticosterone responses, as well as mRNA expression of pertinent genes within the HPA axis. Basal diurnal rhythm of plasma corticosterone concentrations in the adult rat were not affected by prior exposure to neonatal IH. Adults exposed to 10% IH as neonates exhibited an augmented peak ACTH response and a prolonged corticosterone response to restraint stress; however, HPA axis responses to insulin-induced hypoglycemia were not augmented in adults exposed to neonatal IH. Pituitary Pomc, Crhr1, Nr3c1, Nr3c2, Avpr1b, and Hif1a mRNA expression was decreased in adults exposed to neonatal 10% IH. Expression of pertinent hypothalamic and adrenal mRNAs was not affected by neonatal IH. We conclude that exposure to neonatal 10% IH programs the adult HPA axis to hyperrespond to acute stimuli in a stressor-specific manner.

Author List

Chintamaneni K, Bruder ED, Raff H


Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenocorticotropic Hormone
Animals, Newborn
Circadian Rhythm
Disease Models, Animal
Gene Expression Regulation, Developmental
Hypothalamo-Hypophyseal System
Organ Specificity
Pituitary-Adrenal System
RNA, Messenger
Random Allocation
Rats, Sprague-Dawley
Stress, Physiological
Stress, Psychological
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d