title: Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent corticosterone production during hypoxia.
abstract: We have previously demonstrated that the neonatal corticosterone response to acute hypoxia shifts from ACTH independence to ACTH dependence between postnatal days two (PD2) and eight (PD8). Cyclic AMP (cAMP) is the obligatory intracellular second messenger of ACTH action, and we hypothesized that corticosterone production in neonatal rats shifts from a cAMP-independent mechanism to cAMP-dependent mechanism between PD2 and PD8. Plasma ACTH and corticosterone and adrenal cAMP and cGMP responses to acute severe hypoxia (8% O2 for 5, 10, 20, 30, and 180 min) were measured in neonatal rats at PD2, PD8, and PD15. Plasma ACTH and corticosterone were measured by radioimmunoassay, and adrenal cAMP and cGMP were measured by ELISA. Plasma corticosterone-binding globulin (CBG) was measured in normoxic pups by ELISA. The largest corticosterone response was observed in PD2 pups, despite only a small increase in plasma ACTH that was not sustained. The PD2 ACTH-independent increase in corticosterone occurred with no change in adrenal cAMP or cGMP content. Plasma CBG concentration was lowest in PD2 pups. Large corticosterone responses were measured during the first 30 min of hypoxia. Differences in corticosterone responses between PD2 and PD8 pups cannot be attributed to changes in plasma protein binding capacity, and the PD2 corticosterone response is consistent with a nongenomic mechanism of action. We conclude that the sustained corticosterone response to hypoxia in PD2 pups occurs with small and transient ACTH responses and independently of increases in adrenal cAMP or cGMP.
authors.affiliation: Endocrine Research Laboratory, Aurora Research Institute, Aurora St. Luke's Medical Center Milwaukee, Wisconsin ; Department of Medicine, Surgery, and Physiology, Medical College of Wisconsin Milwaukee, Wisconsin.
authors.forename: Karl
authors.initials: K
authors.lastname: Johnson
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bruder
authors.forename: Hershel
authors.initials: H
authors.lastname: Raff
keywords: ACTH; adrenal cortex; cAMP; cGMP; corticosteroid-binding globulin; hypothalamic–pituitary–adrenal axis; newborn; oxygen