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Title: Glucocorticoids and the skin
Author: Teelucksingh, S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Glucocorticoids are the most effective anti-inflammatory agents currently available, but a variety of adverse effects limit their clinical usefulness. This work explores further two facets of the interaction between glucocorticoids and the skin, with the aim of identifying means of reducing glucocorticoid toxicity. (a) Metabolism of glucocorticoid by skin: Human skin is active in the terminal metabolism of cortisol to cortisone, but the biological implications of this process in skin are uncertain. Because there are technical difficulties in dealing with human skin, an animal model, the nude mouse, has been evaluated for its suitability to the study of the metabolism of corticosterone to 11β-dehydrocorticosterone (the homologous reaction in rodents of cortisol to cortisone conversion in man); a process mediated by 11β-hydroxysteroid dehydrogenase. In this model, skin 11β-hydroxysteroid dehydrogenase had an apparent Km for corticosterone of 37 uM. Skin 11β-hydroxysteroid dehydrogenase was up-regulated, in-vivo, by active glucocorticoids and was NADP dependent. By comparison, kidney 11β-hydroxysteroid dehydrogenase had a higher apparent Km (120 uM) for corticosterone, used NAD and NADP with equal facility and was not regulated in-vivo by glucocorticoids. These data suggest that the skin may possess an isoform distinct from that of the kidney. (b) Skin vasoconstrictor response (blanching) to topical glucocorticoids: Glucocorticoids applied topically to human skin produce vasoconstriction in dermal vessels, the degree of which correlates closely with the potency and clinical efficacy of these compounds. Although previous works had noted heterogeneity in blanching responses to glucocorticoids, this was never systematically studied. In qualitative studies, it was shown that skin blanching was inducible by RU-28362, a specific glucocorticoid receptor (type II) agonist and blocked by RU-38486, a glucocorticoid antagonist.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available