Inhibition by Dexamethasone of the in Vivo Pituitary Response to Corticotropin-Releasing Factor (CRF)¹

Abstract

Dexamethasone phosphate in doses ranging from 0 (vehicle control) to 2 μg/rat was injected into both lobes of the anterior pituitary, or into the median eminence or septa region of the brain. Endogenous CRF release was provoked by scald. Dexamethasone bilaterally in the anterior pituitary inhibited ACTH release after scald in doses of 100 ng/lobe or greater. These doses of dexamethasone were ineffective against scald when given intravenously. These results indicated that endogenous CRF-induced ACTH secretion is a corticosteroid-sensitive process, and that the anterior pituitary may be a corticosteroid feedback point. To test this conclusion further, we studied the effect of intrapituitary dexamethasone on the ACTH release induced by exogenous ovine CRF. Intrapituitary dexamethasone was again effective in preventing ACTH release. When similar small doses of dexamethasone were placed in the anterior medial basal hypothalamus, they were effective in stopping the adrenocortical response both to scald and to exogenous CRF. Apparently, spread of dexamethasone from the median eminence to the anterior pituitary can be extensive and rapid. Furthermore, dexamethasone placed in the septal region of the brain, distant from the medial basal hypothalamus, also prevented ACTH release following exogenous CRF. By means of a fluorescent dye, we found that very rapid spread of injected materials to the pituitary occurs after hypothalamic or septal region injections. Though our results may challenge some previous experiments purporting to show the existence of corticosteroid feedback sites in the brain, they do not exclude that possibility. They do establish that the ACTH-releasing process of the pituitary can be inhibited locally by dexamethasone, and therefore that the anterior pituitary may be a corticosteroid inhibitory feedback site. (Endocrinology85: 512, 1969)