Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development.

The hypothalamic-pituitary-adrenal system shows an overall diminished responsiveness throughout ontogeny. Thus, during this period, the sensitivity of the adrenal gland to ACTH is markedly reduced. Furthermore, basal and stress-induced concentrations of corticosterone (CORT), ACTH and hypothalamic secretagogues remain at very low levels. Both structural immaturity and active inhibitory processes appear to underlie this overall hyporesponsiveness. The available data indicate that the characteristic developmental pattern of the HPA system results from multiple regulatory factors acting in conjunction at various levels of the axis. The primary rate-limiting steps, however, are probably at the brain and adrenal levels. The ultimate "goal" appears to be to keep CORT levels within the narrow range of concentrations required for normal development.