OLFACTORY MECHANISMS OF CORTICOSTEROID ACTION

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This research is designed to evaluate the hypothesis that the olfactory mucosa is subject to regulation by adrenal corticosteroid hormones, including the mineralocorticoid aldosterone, as well as glucorticoid hormones. Disorders of adrenal function have been associated with olfactory abnormalities. Furthermore, synthetic adrenal corticosteroids are frequently prescribed for the treatment of clinical olfactory dysfunction. Despite this, little is known regarding the site(s) or mechanism of action of corticosteroids on the olfactory system. Preliminary data for this project has demonstrated the presence of corticosteroid receptors within the olfactory mucosa. initial goals of this project will be to determine the density and distribution of corticosteroid receptors through the use of biochemical, molecular biological, and immunohistochemical techniques. Secondly autoradiographic techniques will be used to determine the density and distribution of the enzyme Na, K-ATPase within the olfactory mucosa. This enzyme, which is regulated by adrenal steroids in many other systems, is present in high levels in tissues specified for secretion and absorption of fluids and electrolytes. Experimentally induced alterations in circulating corticosteroid levels will then be correlated with changes in Na, K-ATPase sites. Third, if adrenal cortical hormones are linked to ion flux and olfactory secretion through the regulation of Na, K-ATPase, they will have an effect on olfactory mucus ion composition and possibly, sensory transduction. Atomic spectrophotometry will be used to analyze changes in olfactory mucus ion concentration associated with alterations in circulating corticosteroids.