Neural circuitry in the regulation of adrenal corticosterone rhythmicity

Adrenal cortical secretion of glucocorticoids is an essential adaptive response of an organism to stress. Although the hypothalamic-pituitary-adrenal axis regulates the adrenal cortex via release of ACTH, there is strong evidence supporting a role for sympathetic innervation in modulating adrenal glucocorticoid secretion. The dissociation between changes in ACTH and glucocorticoids under non-stress and stress conditions has reinforced the concept that neural control of the adrenal cortex acts to modulate steroidogenic responses to circulating ACTH. A dual control of the adrenal cortex has been implicated in the prominent circadian rhythm in glucocorticoids. However, the central neural substrate for circadian changes in glucocorticoids that are mediated by peripheral neural innervation of the adrenal cortex has not been conclusively delineated. The hypothesis to be addressed is that neurons in the paraventricular nucleus of the hypothalamus receive input from the suprachiasmatic nucleus and project to sympathetic preganglionic neurons in the spinal cord to provide inhibitory and excitatory input to the adrenal cortex that drives the circadian rhythm. This review examines anatomical and physiological evidence that forms the basis for this putative neural circuit.