Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries...

Studies concerning the identification of Secretogranin II (SgII) and its processed forms in human pituitary remain scarce since no anti-human SgII antisera has been available. In the present report, a specific hSgII antiserum was used in immunohistochemistry experiments to determine the distribution of SgII in normal anterior pituitaries and pituitary adenomas (5 gonadotroph, 3 non-functioning and 5 mammotroph tumors). In normal pituitaries SgII was detected in gonadotrophs, thyrotrophs and corticotrophs but was absent from somatotrophs and mammotrophs. In tumor tissues, the SgII protein was found in gonadotroph and non-functioning adenomas but not in the mammotroph tumors. Northern blot analyses demonstrated the same 2.5 kb SgII mRNA species in all types of tumors as in normal anterior pituitaries. In Western blotting experiments, apart from the 97 K polypeptide. SgII antiserum detected two lower Mr proteins, 46 K and 31 K. These were observed in gonadotroph and in non-functioning adenomas and were absent from the mammotroph adenomas. Four new antisera were raised against sequential regions of SgII (N-terminal, two internal and C-terminal sequences). Western blotting experiments revealed that both the 46 K and 31 K polypeptides arose from the second half (C-terminal) of the molecule, thus suggesting that SgII may be processed by cleavage of short N-terminal polypeptides not detected in our conditions. Our results indicate that SgII may represent not only a valuable histological marker for non-functioning pituitary adenomas, but also a pertinent tool to study the proteolytic processing mechanisms in various neuroendocrine tumors.