Coordinate, equimolar secretion of smaller peptide products derived from pro-ACTH/endorphin by mouse pituitary tumor cells.
The secretion of peptide products derived from pro-ACTH/endorphin was examined with several radioimmunoassays and with polyacrylamide gel analyses of immunoprecipitates of radioactively labeled peptides. In studies using a mouse pituitary tumor cell line the accumulation of each of the four molecular forms of adrenocorticotropic hormone (ACTH) in tissue culture medium was shown to be a linear function of time. No evidence for self inhibition of secretion by accumulated, secreted peptides (i.e., ultra-short feedback) was found. Furthermore, synthetic human ACTH and synthetic camel beta-endorphin did not alter secretion of peptides when added to the culture medium at levels up to 10,000 times physiological. Stimulation of the release of ACTH-, endorphin-, lipotropin-, and 16k fragment immunoreactive material by norepinephrine was fully blocked by cobalt; by this criterion, stimulated release was calcium dependent. All the smaller molecules derived from the pro-ACTH/endorphin common precursor were secreted in equimolar amounts under all circumstances tested, within the precision of these studies (+/- 11%). Norepinephrine and cobalt did not significantly alter the secretion of pro-ACTH/endorphin and ACTH biosynthetic intermediate. The stimulation of secretion by norepinephrine and inhibition of secretion by cobalt was restricted to the lower molecular weight products derived from pro-ACTH/endorphin: glycosylated and nonglycosylated ACTH(1-39); beta-lipotropin, beta-endorphin, and gamma-lipotropin; and 16k fragment.
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004723:Endorphins / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011333:Pro-Opiomelanocortin; D011498:Protein Precursors / Q000378:metabolism*; D008083:beta-Lipotropin / Q000378:metabolism
D004723:Endorphins; D010455:Peptides; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D008083:beta-Lipotropin