Atrial natriuretic factor (ANF), a 28 amino acid peptide hormone, is the major secretory product of the heart. Because of its diuretic, natriuretic and vasodilating activities, this peptide may be involved in the maintenance of proper fluid and electrolyte balance and blood pressure control. In order to study the transcriptional regulation of ANF, we have isolated the rat ANF gene and we have established a system of cardiocytes in primary cell culture for studies on the hormonal, tissue-specific and developmental regulation of the ANF gene. Using this in vitro system, as have demonstrated that thyroid hormone increases ANF mRNA levels about 2- to 4-fold in atrial and ventricular cells in primary cardiocyte cell cultures, respectively. Similarly, glucocorticoids augment by about 3-fold both atrial and ventricular ANF mRNA levels in cardiac cells in culture. Glucocorticoids exert this effect at the transcriptional level probably via the binding of glucocorticoid receptor to a DNA element in the distal 5$ sp prime$-flanking sequences of the gene as suggested by DNA-mediated transfection studies in cardiocyte cultures. In order to better understand the mechanisms governing the cardiac-specific as well as developmental expression of the ANF gene, we have analyzed ANF promoter sequences by transient transfection studies in primary cardiocyte cultures. Our data show that the ANF promoter is active only in cells of cardiac origin. Moreover, up to $-$1.6 kb of 5$ sp prime$ upstream sequences are necessary for full expression of the ANF gene in cardiac cells. Within these sequences, two particular elements, a proximal and a distal, are necessary for full ANF transcriptional activity. The proximal element can confer cardiac specificity to an otherwise non tissue-specific heterologous promoter. Further upstream sequences, between $-$2.5 and $-$1.6 kb appear to be implicated in the developmental control of ANF gene expression, as assessed by differential activity in 1 and 4 d
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74556 |
| Date | January 1990 |
| Creators | Argentin, Stefania |
| 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: 001167902, proquestno: AAINN66454, Theses scanned by UMI/ProQuest. |
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