Chromogranin A (CgA) is the major member of a family of acidic secretory glycoproteins (collectively known as granins) that are expressed in all endocrine and neuroendocrine cells. Granins have been proposed to play multiple roles, both intracellular and extracellular, in the secretory process. The regulation of synthesis and secretion of CgA in primary cultures of bovine parathyroid cells was studied and compared to that of parathyroid hormone (PTH). The effects of both extracellular calcium and the active metabolite of vitamin D$ sb3$, 1,25-dihydroxyvitamin D$ sb3$ (1,25(OH)$ rm sb2D sb3$) were shown to modulate CgA synthesis and secretion in the parathyroid. Whereas a reduced medium calcium level stimulated both CgA and PTH secretion, it had no effect on CgA mRNA levels. In contrast, 1,25(OH)$ rm sb2D sb3$ stimulated CgA mRNA levels by increasing the CgA gene transcription rate. Thus, 1,25(OH)$ rm sb2D sb3$ had opposite actions on the CgA and PTH genes in the parathyroid cell. The relationship between 1,25(OH)$ rm sb2D sb3$-stimulated CgA mRNA levels and total CgA protein levels (intracellular and extracellular) was not simple. Although 1,25(OH)$ rm sb2D sb3$ increased CgA mRNA levels several-fold, there was only a modest increase in CgA protein. This was the result of a specific effect of 1,25(OH)$ rm sb2D sb3$ on decreasing the translational efficiency of CgA mRNA as demonstrated by an increased ribosome transit time for CgA mRNA. To better understand the functional domains of CgA, and its evolution, and to study the basis of its neuroendocrine cell-specific gene expression, the human CgA gene was cloned and characterized. It spans 15 kb and contains eight exons. There is high conservation between the human, mouse, and bovine CgA genes with respect to exon number and placement of exon/intron borders. Transient transfection studies with constructs containing portions of the 5$ sp prime$ gene flanking region upstream of a chloramphenicol acetyl transferase rep
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41304 |
| Date | January 1993 |
| Creators | Mouland, Andrew |
| Contributors | Hendy, Geoffrey N. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001351899, proquestno: NN91839, Theses scanned by UMI/ProQuest. |
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