The present thesis has examined in detail the dynamics of adrenomedullary glucocorticoid (GC) receptors at various concentrations of steroid, the regulation of levels of receptor following various treatments, and the regulation of phenylethanolamine N-methyltransferase (PNMT) activity following acute exposure to GCs and various time delays, providing evidence that GC regulation of adrenomedullary catecholamine biosynthesis is more dynamic than was classically thought. We report that adrenomedullary GC receptors are translocated, both in response to nM concentrations of GCs, and in response to higher concentrations of GCs encountered by the glands during stress. We show that long-term increases in cyclic nucleotide second messengers are able to decrease GC receptor binding in adrenal medullary cells, via a mechanism independent of released cortisol, and provide the first evidence that changes in adrenomedullary GC receptor levels are reflected in an alteration in a GC-mediated function, i.e. induction of PNMT. We also provide novel in vitro evidence for the regulation of adrenomedullary PNMT activity, following a necessary lag period, by acute changes in both cortisol and nicotine. In addition, our in vitro studies are supported by our in vivo findings which show increases in adrenal tyrosine hydroxylase and PNMT activity 18h following a single episode of mild acute stress (20 min restraint) in rats.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41278 |
| Date | January 1993 |
| Creators | Betito, Katia |
| Contributors | Boksa, Patricia (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 (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001351737, proquestno: NN91818, Theses scanned by UMI/ProQuest. |
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