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Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat. Am J Physiol Regul Integr Comp Physiol 2008 Oct;295(4):R1195-203



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2-s2.0-57349083071   29 Citations


Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O(2) for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O(2) for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response ( approximately 3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O(2) saturation (SPo(2)) to approximately 80% and also decreased body temperature by 5-6 degrees C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8).

Author List

Bruder ED, Taylor JK, Kamer KJ, 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

Adrenal Glands
Adrenocorticotropic Hormone
Animals, Newborn
Body Temperature
Gene Expression Regulation, Developmental
Heart Rate
Hypothalamo-Hypophyseal System
Neuropeptide Y
Pituitary Gland, Anterior
Pituitary-Adrenal System
Proto-Oncogene Proteins c-fos
RNA, Messenger
Rats, Sprague-Dawley
Receptors, Corticotropin-Releasing Hormone
Receptors, Glucocorticoid
Receptors, LDL
Reverse Transcriptase Polymerase Chain Reaction
Sex Factors
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d