Involvement of the calcium-binding protein secretagogin in pituitary adenoma hormone production

Calcium is a potent intracellular signal transducer whose fluctuations control numerous cellular processes among them hormone production. Secretagogin (SCGN) is an intracytoplasmatic protein belonging to the EF-hand calcium binding protein superfamily, which was initially isolated from a human pancreatic cDNA library and was shown to be involved in the regulation of insulin synthesis and secretion. Since SCGN was also detected in neuroendocrine cells in the anterior pituitary, we have studied the expression of SCGN both in normal and tumoral pituitary and have started to elucidate its role in pituitary cells. Our preliminary results obtained by Real time PCR analysis showed the expression of SCGN in a group of 4 normal human anterior pituitary glands and in 26 different pituitary adenomas. In the tumours, SCGN mRNA was downregulated in 2/4 somatotrophinomas, 6/7 nonfunctioning pituitary adenomas, 4/6 prolactinomas, 3/6 corticotrophinomas and 2/2 thyrotrophinomas when compared to the expression in normal pituitary tissue. The co-transfection of a rat SCGN expression plasmid with prolactin-luc reporter plasmid, GH-luc plasmid and POMC-luc reporter plasmid, respectively in mammosomatotroph GH3 cells and in corticotroph AtT-20 cells, showed that SCGN overexpression was able to induce a 46% increase in the activity of the prolactin gene promoter and a 60% increase in the activity of the GH gene promoter, while in AtT-20 cells the activity of POMC gene promoter showed an increase of 66%. The analysis of the different promoter elements showed an activation of CRE element in GH3 cells after SCGN plasmid co-transfection and an increase in cAMP production. In AtT-20 cells SCGN plasmid co-transfection was able to induce an increase in the activities of AP-1, Nbr-E and NurrRE elements, which was also accompanied by an increase in cAMP production. These preliminary findings suggest the involvement of SCGN in controlling the synthesis of pituitary hormones, therefore constituting a potential target for inhibiting the hormone production.