Central activity of glucocorticoids and glucocorticoid receptors in the genetically obese zucker rat (fa/fa)
Central activity of glucocorticoids and glucocorticoid receptors in the genetically obese zucker rat (fa/fa)
The genetic obesity of the fa/fa rat is characterised by increased weight gain, hyperadiposity, hyperphagia, hyperinsulinaemia and reduced sympathetic drive to brown adipose tissue. The obesity is abolished by adrenalectomy and restored by glucocorticoids, indicating a role for corticosterone in the expression of the syndrome. Corticosterone concentrations in serum, whole brain and specific brain regions were found to be normal in obese rats. Activities of glucocorticoid-sensitive enzymes, glycerol 3-phosphate dehydrogenase, glutamine synthetase and tyrosine hydroxylase, were elevated in the hippocampus and hypothalamus of the obese rat. Increased activity of corticosterone in these brain regions is inferred, suggesting that in the absence of elevated hormone levels the obese rat shows increased sensitivity to corticosterone action. The type II glucocorticoid receptor antagonist, RU486, reversibly abolished obesity through increases in brown adipose tissue thermogenesis and decreases in energetic efficiency. The drug appeared to act centrally, and obesity was abolished independently of changes in food intake. A role for central type II receptors in the development of obesity is suggested. Type II and type I glucocorticoid receptor numbers were elevated in the hippocampus and hypthalamus of obese rats. Type II sites in the liver were present in normal numbers. The basis of increased type II receptor numbers in the brain appeared to be a defect of regulation by corticosterone. A possible role for glucocorticoid receptors in the central modulation of autonomic balance is discussed, with the hypothesis being that increased corticosterone action in the hypothalamus leads to a suppression of corticotropin releasing factor synthesis.
University of Southampton
Langley, Simon Cooke
94f4c1b1-0dbe-4bd4-8e2f-bba55a0f72ee
1990
Langley, Simon Cooke
94f4c1b1-0dbe-4bd4-8e2f-bba55a0f72ee
Langley, Simon Cooke
(1990)
Central activity of glucocorticoids and glucocorticoid receptors in the genetically obese zucker rat (fa/fa).
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The genetic obesity of the fa/fa rat is characterised by increased weight gain, hyperadiposity, hyperphagia, hyperinsulinaemia and reduced sympathetic drive to brown adipose tissue. The obesity is abolished by adrenalectomy and restored by glucocorticoids, indicating a role for corticosterone in the expression of the syndrome. Corticosterone concentrations in serum, whole brain and specific brain regions were found to be normal in obese rats. Activities of glucocorticoid-sensitive enzymes, glycerol 3-phosphate dehydrogenase, glutamine synthetase and tyrosine hydroxylase, were elevated in the hippocampus and hypothalamus of the obese rat. Increased activity of corticosterone in these brain regions is inferred, suggesting that in the absence of elevated hormone levels the obese rat shows increased sensitivity to corticosterone action. The type II glucocorticoid receptor antagonist, RU486, reversibly abolished obesity through increases in brown adipose tissue thermogenesis and decreases in energetic efficiency. The drug appeared to act centrally, and obesity was abolished independently of changes in food intake. A role for central type II receptors in the development of obesity is suggested. Type II and type I glucocorticoid receptor numbers were elevated in the hippocampus and hypthalamus of obese rats. Type II sites in the liver were present in normal numbers. The basis of increased type II receptor numbers in the brain appeared to be a defect of regulation by corticosterone. A possible role for glucocorticoid receptors in the central modulation of autonomic balance is discussed, with the hypothesis being that increased corticosterone action in the hypothalamus leads to a suppression of corticotropin releasing factor synthesis.
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Published date: 1990
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Local EPrints ID: 460690
URI: http://eprints.soton.ac.uk/id/eprint/460690
PURE UUID: ef981784-68c4-486b-90e1-29eedfbe7154
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Date deposited: 04 Jul 2022 18:27
Last modified: 23 Jul 2022 00:58
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Author:
Simon Cooke Langley
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