The regulation of human 11b-hydroxysteroid dehydrogenase
The regulation of human 11b-hydroxysteroid dehydrogenase
This thesis describes the development of three novel techniques for the sensitive estimation of unconjugated corticosteroids in biological fluids. Two utilise reversed phase HPLC with either fluorescence detection subsequent to derivatisation with 7-(carboxymethoxy)-4-methylcoumarin or UV absorbance detection. The third comprises a novel radioimmunoassay for urinary free cortisone. These techniques were used to make a comparison of urinary free cortisol:cortisone ratios and total cortisol:cortisone metabolite ratios as indices of renal 11β-HSD2 activity.
Previous studies of 11β-HSD suggest that the enzyme is hormonally regulated. Extensive studies of the steroidogenic and steroid metabolising properties of the choriocarcinoma cell line, JEG-3, have established this cell line as a model of steroid metabolism and particularly 11β-HSD2 activity in trophoblastic tissue. However, few studies have attempted a systematic investigation of the hormonal regulation of 11β-HSD2 in these cells. Thus this thesis describes a series of novel investigations of the regulation of 11β-HSD1 in skeletal myoblasts and 11β-HSD2 in JEG-3 by steroid and peptide hormones and by pro-inflammatory and colony stimulating cytokines. Finally, this thesis describes the strong associations between glucocorticoid receptor and 11β-HSD1 expression and key features of the metabolic syndrome in human skeletal myoblasts from a cohort of men with varying degrees of insulin resistance adiposity and blood pressure. Moreover, these studies also suggest a role of 11β-HSD1 in the regulation of glucocorticoid hormone action in skeletal muscle and highlight the significance of dysregulation of isoforms of 11β-HSD in the aetiology of the metabolic syndrome.
University of Southampton
Donovan, Stephen James
e9aaec68-73c9-4e32-aea9-d842d6dafb24
2000
Donovan, Stephen James
e9aaec68-73c9-4e32-aea9-d842d6dafb24
Donovan, Stephen James
(2000)
The regulation of human 11b-hydroxysteroid dehydrogenase.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis describes the development of three novel techniques for the sensitive estimation of unconjugated corticosteroids in biological fluids. Two utilise reversed phase HPLC with either fluorescence detection subsequent to derivatisation with 7-(carboxymethoxy)-4-methylcoumarin or UV absorbance detection. The third comprises a novel radioimmunoassay for urinary free cortisone. These techniques were used to make a comparison of urinary free cortisol:cortisone ratios and total cortisol:cortisone metabolite ratios as indices of renal 11β-HSD2 activity.
Previous studies of 11β-HSD suggest that the enzyme is hormonally regulated. Extensive studies of the steroidogenic and steroid metabolising properties of the choriocarcinoma cell line, JEG-3, have established this cell line as a model of steroid metabolism and particularly 11β-HSD2 activity in trophoblastic tissue. However, few studies have attempted a systematic investigation of the hormonal regulation of 11β-HSD2 in these cells. Thus this thesis describes a series of novel investigations of the regulation of 11β-HSD1 in skeletal myoblasts and 11β-HSD2 in JEG-3 by steroid and peptide hormones and by pro-inflammatory and colony stimulating cytokines. Finally, this thesis describes the strong associations between glucocorticoid receptor and 11β-HSD1 expression and key features of the metabolic syndrome in human skeletal myoblasts from a cohort of men with varying degrees of insulin resistance adiposity and blood pressure. Moreover, these studies also suggest a role of 11β-HSD1 in the regulation of glucocorticoid hormone action in skeletal muscle and highlight the significance of dysregulation of isoforms of 11β-HSD in the aetiology of the metabolic syndrome.
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Published date: 2000
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Local EPrints ID: 464124
URI: http://eprints.soton.ac.uk/id/eprint/464124
PURE UUID: 620909de-2526-46e7-a673-808c3746248c
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Date deposited: 04 Jul 2022 21:19
Last modified: 16 Mar 2024 19:16
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Author:
Stephen James Donovan
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