Acute hypoxia in neonatal rats: a novel ACTH‐and cAMP‐independent control of adrenal function

Abstract

The hypothalamic‐pituitary‐adrenal (HPA) axis plays a critical role in the adaptation to neonatal hypoxia. The classic adrenocortical response involves ACTH‐stimulated corticosterone (Cort) synthesis mediated by increased cAMP. We previously demonstrated that, in the neonatal rat, the Cort response to acute hypoxia shifts from ACTH‐independence to ACTH‐dependence between postnatal day (PD) 2 and 8. We now correlate plasma ACTH and Cort responses with adrenal cAMP content from PD2 and PD8 rats exposed to acute hypoxia. In PD2 rats, hypoxia elicited a minimal increase in plasma ACTH, no change in adrenal cAMP content, but a robust increase in plasma Cort. In PD8 rats, hypoxia elicited large increases in plasma ACTH, adrenal cAMP content, and plasma Cort, consistent with the classic mechanism of adrenocortical control. Preliminary results using adrenocortical cells in vitro to bioassay plasma corticotropic activity showed a hypoxia‐induced 3.5‐fold increase in PD2 plasma and a 1.7 fold increase in PD8 plasma, suggesting a humoral mechanism of stimulation of Cort in PD2 rats. The data indicate that the robust plasma Cort response to hypoxia in the PD2 rat does not require ACTH‐mediated increases in cAMP production in the adrenal. This ACTH‐and cAMP‐independent control of adrenocortical function, exhibited only in the newborn rat, may be due to a novel hormonal mechanism of zona fasciculata control. NSF IOS1025199