Adrenocorticotropic hormone and corticosterone responses to acute hypoxia in the neonatal rat: effects of body temperature maintenance

Abstract

The corticosterone response to acute hypoxia in neonatal rats develops in the 1st wk of life, with a shift from ACTH independence to ACTH dependence. Acute hypoxia also leads to hypothermia, which may be protective. There is little information about the endocrine effects of body temperature maintenance during periods of neonatal hypoxia. We hypothesized that prevention of hypothermia during neonatal hypoxia would augment the adrenocortical stress response. Rat pups separated from their dams were studied at postnatal days 2 and 8 (PD2 and PD8). In one group of pups, body temperature was allowed to spontaneously decrease during a 30-min prehypoxia period. Pups were then exposed to 8% O(2) for 3 h and allowed to become spontaneously hypothermic or externally warmed (via servo-controlled heat) to maintain isothermia. In another group, external warming was used to maintain isothermia during the prehypoxia period, and then hypoxia with or without isothermia was applied. Plasma ACTH and corticosterone and mRNA expression of genes for upstream proteins involved in the steroidogenic pathway were measured. Maintenance of isothermia during the prehypoxia period increased baseline plasma ACTH at both ages. Hypothermic hypoxia caused an increase in plasma corticosterone; this response was augmented by isothermia at PD2, when the response was ACTH-independent, and at PD8, when the response was ACTH-dependent. In PD8 rats, isothermia also augmented the plasma ACTH response to hypoxia. We conclude that maintenance of isothermia augments the adrenocortical response to acute hypoxia in the neonate. Prevention of hypothermia may increase the stress response during neonatal hypoxia, becoming more pronounced with increased age.

Programming of the Hypothalamic-Pituitary-Adrenal Axis by Neonatal Intermittent Hypoxia: Effects on Adult Male ACTH and Corticosterone Responses Are Stress Specific

“…It has previously been suggested there is a protective effect of hypoxia-induced hypothermia in the neonate (18,24). We measured a subtle yet significant decrease in body temperature during neonatal hypoxia in the neonates exposed to 10% IH, but not 5% IH.…”

Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent corticosterone production during hypoxia

“…These experiments showed no change in Star mRNA expression in PD2 (Bruder et al. , ). However, transcriptional changes in Star mRNA are not necessarily required for an increase in corticosterone production because of the release of labile stores of StAR protein (Ariyoshi et al.…”

“…,b, ; Bruder et al. , ). Our primary focus has been to evaluate the change in control of adrenal corticosterone production that shifts from ACTH independence to ACTH dependence between PD2 and PD8.…”

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

“…First, it is possible that increased corticosterone production is stimulated by IH-induced sympathetic drive to the adrenal cortex, which is innervated by postganglionic sympathetic neurons (25). This innervation is present and functional in the immature adrenal gland (3,4). Second, the response may be due to increased sensitivity of the adrenal cortex to very small changes in ACTH in the PD2 pups.…”

“…PD8 has been described as an important age in the neonate. By PD8, physiological controls mature into those similar to an adult rat (3,4,29). This could also be an indication that the mechanism of body temperature control and heart rate are connected via the autonomic nervous system (28).…”