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 hypothalamic-pituitary-adrenal axis is not well understood. The direct anti-inflammatory activities of lipocortins (LCs) have suggested a role for 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 from AtT-20 D16:16 corticotrophs. Using the same cell line we have tested whether other exogenous rhLCs or native LC extracted from polymorphonucleate neutrophils (neLC), likely LC1, have an effect on ACTH secretion. It is shown that: (1) basal release was not affected by a short-term incubation with neLC; (2) secretion induced by corticotropin-releasing factor (CRF) and other secretagogues (phorbol ester, potassium ion or calcium ionophore) was inhibited by neLC; (3) GC inhibition of CRF-stimulated release was reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment 212-234 of rhLC5 were without effect. 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 secretion.
Pompeo
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A
Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro Chieti, Italy.
Luini
A
A
Hirata
F
F
Baldassarre
M
M
Buccione
R
R
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017302:Annexins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology
D017302:Annexins; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D007476:Ionophores; D011994:Recombinant Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium