Pituitary-dependent and -independent secretion of CS caused by bacterial endotoxin in rats

Injection of bacterial endotoxin [lipopolysaccharide (LPS)] or immobilization stress increased serum levels of ACTH with a concomitant increase in the levels or corticosterone (CS) of rats. LPS also caused a significant increase in the serum CS levels of hypophysectomized rats. In contrast, immobilization stress-induced CS release was abolished completely in these rats. Injection of histamine, a possible mediator of LPS-induced CS secretion, provoked a significant increase in the serum CS levels of hypophysectomized rats. Neither histamine nor LPS had any appreciable effect on production or release of CS by cultured adrenal cells. These results suggest that LPS-induced CS secretion is largely dependent on hypophysial ACTH release but it also depends, in part, on an extrapituitary mechanism and that the LPS-induced pituitary-independent secretion of CS is mediated by histamine produced in the peripheral tissues. On the other hand, stress-provoked CS secretion is absolutely dependent on the pituitary-adrenocortical system.