NEUTROPHIL EXTRACTED LIPOCORTIN INHIBITS CORTICOTROPIN SECRETION IN THE ATT-20 D16 16 CLONAL MOUSE PITUITARY CELL-LINE - LIPOCORTIN INHIBITION OF ACTH RELEASE IN-VITRO/

The mechanism of short-term glucocorticoid (GC) inhibition of the hypo thalamic-pituitary-adrenal axis is not well understood. The direct ant i-inflammatory activities of lipocortins (LCs) have suggested a role f or them as extra-and intracellular mediators of the biological effects of GCs. It has been reported that recombinant human (rh) LC1 inhibits corticotropin (ACTH) release from pituitary tissue in vitro but not f rom AtT-20 D16:16 corticotrophs. Using the same cell line we have test ed whether other exogenous rhLCs or native LC extracted from polymorph onucleate neutrophils (neLC), likely LC1, have an effect on ACTH secre tion. It is shown that: (1) basal release was not affected by a short- term incubation with neLC; (2) secretion induced by corticotropin-rele asing factor (CRF) and other secretagogues (phorbol ester, potassium i on or calcium ionophore) was inhibited by neLC; (3) GC inhibition of C RF-stimulated release was reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment 212-234 of rhLC5 were without effec t. Thus, only neLC is effective on AtT-20 D16:16 cells, suggesting for this annexin a role in the early phase GC inhibition of ACTH secretio n. (C) 1997 Elsevier Science B.V.