Glucocorticoid receptor binding characteristics in rat genetic models of hypertension and in normal subjects of known glucocorticoid receptor genotype

Panarelli, Maurizio (1995) Glucocorticoid receptor binding characteristics in rat genetic models of hypertension and in normal subjects of known glucocorticoid receptor genotype. PhD thesis, University of Glasgow.

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The evidence of a familial component in the development of hypertension has been discussed in its socio-economical, genetical and hormonal aspects. Of the endocrine influences, the activity of the adrenal cortex and the way in which both mineralocorticoids and glucocorticoids interact with their target tissues has been evaluated. It has been suggested that this interaction may vary in a genetically determined manner. Recent studies suggested that the restriction fragment length polymorphism (RFLP) of the glucocorticoid receptor (GR) is associated with differences of blood pressure. Subjects from the Ladywell district of Edinburgh who were homozygous for one GR genotype had higher blood pressure than those homozygous for the other. The hypothesis that the receptor genotype might be associated with phenotypic differences in glucocorticoid responsiveness, which in turn could contribute to the development of hypertension, was drawn. This hypothesis has been investigated in strains of rat prone to develop hypertension and in a group of normotensive male subjects characterised for GR RFLP genotype. The investigation first required the adaptation, validation and use of a number of biochemical and cell biology techniques. A new method of measuring glucocorticoid potency has been developed, based on the ability of glucocorticoids to inhibit the translation of the lysozyme gene. In addition, a large body of information on variables concerned with electrolyte homeostasis and the control of intermediary metabolism were collected. Many of the variables correlated independently of the receptor polymorphism. The results suggested a complex interaction of mineralocorticoid and glucocorticoid functions in the pathogenesis of hypertension. In conclusion, studies in rats with genetic hypertension and in patients strongly indicate that glucocorticoid sensitivity may be a contributory factor in essential hypertension. If this is the case, then hypertension - or predisposition to hypertension - should be associated with a constellation of glucocorticoid sensitivity-related changes. If sensitivity is impaired, mineralocorticoid-like changes may result. If sensitivity is increased, glucocorticoid-dependant variables should change. Although neither hypothesis has been absolutely established by the experiments described in this thesis, they have provided some valuable guidelines for future studies. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Genetics.
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Fraser, Dr. R. and Kenyon, Dr. C.J.
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-71702
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 27 Oct 2021 09:30
Thesis DOI: 10.5525/gla.thesis.71702

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