Response of the HPA Axis to Intermittent Hypoxia in the Neonatal Rat: ACTH, Corticosterone, and the Expression of Adrenal mRNAs

Abstract

Apnea is the temporary cessation of respiratory airflow and is a common cause of intermittent hypoxia (IH) in the premature infant. We hypothesized that IH elicits a stress response in the neonate and alters mRNA expression for critical proteins involved in adrenocortical function. Postnatal day 2 (PD2), PD8, and PD12 rat pups were exposed to 6 cycles of 30 sec of IH (3% O2) over 60 min, and blood samples were obtained at the 3rd (30 min) and 6th (60 min) cycle. Plasma ACTH and corticosterone increased significantly in PD8 and PD12 pups exposed to IH. Interestingly, plasma corticosterone increased in the PD2 pups even though plasma ACTH remained unchanged. Expression of adrenal StAR and Ldlr mRNA increased in PD2 pups exposed to IH, but were not affected in PD8 or PD12 pups. Expression of adrenal Mc2R mRNA decreased in all age groups exposed to IH. IH resulted in profound bradycardia and a decrease in body temperature. We conclude that IH in PD2 pups elicits an adrenocortical response not mediated by ACTH, but associated with an increase in the expression of specific adrenal mRNAs. In PD8 and PD12 pups, the adrenal response is ACTH dependent like an adult. Using the PD2 rat as a model of extreme prematurity in the human, we suggest the existence of a unique non‐ACTH controller of adrenal function during IH.