Autocrine Regulation of Parathyroid Secretion: Inhibition of Secretion by Chromogranin-A (Secretory Protein-I) and Potentiation of Secretion by Chromogranin-A and Pancreastatin Antibodies*

Chromogranin-A, also referred to as secretory protein-I, is a 50-kDa protein present in and secreted by most endocrine cells together with the native hormone. Porcine chro- mogranin-A contains a sequence identical to pancreastatin, sug- gesting that it is the precursor of pancreastatin. Pancreastatin is a potent inhibitor of parathyroid gland secretion, and it and chromogranin-A inhibit glucose-stimulated insulin release by the pancreas. It is possible that chromogranin-A, pancreastatin, or a related peptide is a physiological inhibitor of secretion by the parathyroid as well as other endocrine glands. As a test of this hypothesis, parathyroid cells in culture were incubated with purified porcine chromogranin-A or antisera to chromogranin- A and pancreastatin. In the absence of exogenous chromogranin- A or antisera, secretion of chromogranin-A and PTH at 0.5 mM Ca 2+ was about twice that at 3.0 mM Ca 2+ . When intact chro- mogranin-A was added to the incubation medium at 0.5 mM Ca 2+ , secretion was reduced to the basal level obtained at 3.0 mM Ca 2+ . Chromogranin-A did not affect the secretion of cells incubated at 3.0 mM Ca 2+ . At 1 h of incubation, 100 nM chro- mogranin-A was equivalent in potency to 1 nM pancreastatin, but after 3 h the two agents were equipotent. This suggests that chromogranin-A was processed into biologically active peptide(s) during incubation. Antisera directed against chromogranin-A or pancreastatin potentiated the secretion of both chromogranin- A and PTH at 0.5 mM, but not 3.0 mM, Ca 2+ . This stimulatory action of the antisera was dose dependent from 1:3200 to 1:400 final dilution, was effective within 2 h, and did not shift the Ca 2+ set-point for glandular secretion. These results are consonant with chromogranin-A-derived peptides serving as an autocrine inhibitor of parathyroid gland secretion. (Endocrinology 127: 1329-1335, 1990)