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.
Endocrine Unit, Massachusetts General Hospital, Boston 02114.
A R
AR
Gwosdow
J A
JA
Spencer
N A
NA
O'Connell
A B
AB
Abou-Samra
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010911:Pituitary Neoplasms; D011494:Protein Kinases / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D011494:Protein Kinases