Interleukin-1 activates protein kinase A and stimulates adrenocorticotropic hormone release from AtT-20 cells.

Studies from this and other laboratories have shown that interleukin-1 (IL-1) stimulates ACTH secretion directly from AtT-20 cells. The present studies were conducted to determine the signal transduction mechanisms activated by IL-1 to stimulate ACTH release. IL-1 significantly (P < 0.05) elevated ACTH release after incubation periods of 4, 8, and 24 h. IL-1-induced ACTH release was not additive to that of CRF, cholera toxin, 8-bromo-cAMP, or forskolin. In contrast, IL-1 and the phorbol ester phorbol 12-myristate 13-acetate together produced a greater increase (P < 0.05) in ACTH release than either agent alone. IL-1 did not stimulate cAMP accumulation at any time period between 5 min and 24 h and did not affect cAMP accumulation induced by CRF, cholera toxin, or forskolin. The lack of additivity between IL-1 and CRF, cholera toxin, 8-bromo-cAMP, and forskolin suggests that IL-1 stimulates ACTH release by a pathway that shares some common step(s) with CRF. Because IL-1 did not affect cAMP accumulation, the effect of IL-1 on protein kinase A (PKA) was investigated. IL-1 began to increase (P < 0.05) PKA activity at 15 min and remained elevated for 2 h before returning to control levels. IL-1 stimulation of PKA and the lack of additivity between IL-1 and CRF, forskolin, and cholera toxin indicate that PKA is the intracellular mediator used by IL-1 to stimulate ACTH release in AtT-20 cells.