Deoxycorticosterone acetate (DOCA) and 9 alpha-fluorocortisol acetate (9 alpha-F-Cac) can be modified by the introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives). Such a modification markedly changes the effect of the steroids on urinary excretion of Na+ and K+. Since 6-7 reduction of DOCA and 9 alpha-F-Cac substantially reduces affinity for Type II receptors but not Type I receptors, 6-dehydro-derivatives will thus bind preferentially to receptors influencing the retention of sodium (the "mineralocorticoid" or Type I receptor), and compete with mineralocorticoids for such receptors. We interpret the increase in both natriuresis and kaliuresis when mineralocorticoids and their dehydro-derivatives are administered together as evidence for a Type II receptor mediation of these ion fluxes.
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http://dx.doi.org/10.1016/0022-4731(85)90021-4 | DOI Listing |
Arch Int Physiol Biochim
April 1989
Institut de Chimie; CHU, Université de Liège.
The introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives) of deoxycorticosterone acetate (DOCA), cortisol-21-acetate, 9 alpha-fluorocortisol-21-acetate (9 alpha-F-C-ac) and aldosterone-21-acetate substantially reduces affinity for Type II receptors but not for Type I receptors. Such a modification changes the effect of these steroids on urinary excretion of Na+ and K+. 6-Dehydro-derivatives will thus bind preferentially to receptor Type I inducing the retention of sodium and compete with mineralocorticoids for such receptors.
View Article and Find Full Text PDFThis paper reports the crystal structure of the propanol solvate of 9 alpha-fluorocortisol acetate, which crystallizes in the monoclinic space group P21 [a = 7.470 (6), b = 14.78 (1), c = 12.
View Article and Find Full Text PDFIn order to investigate the possible role of mineralocorticoid in the regulation of digoxin-like substance (DLS), 9 alpha-fluorocortisol (9-F) was administered to 6 healthy men and urinary excretion of DLS was measured. The administration of 0.6 mg of 9-F caused slight increases in body weight and blood pressure and significant decreases in urinary Na excretion, plasma renin activity and plasma aldosterone, which indicate the expansion of extracellular fluid (ECF) volume by 9-F administration.
View Article and Find Full Text PDFDeoxycorticosterone acetate (DOCA) and 9 alpha-fluorocortisol acetate (9 alpha-F-Cac) can be modified by the introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives). Such a modification markedly changes the effect of the steroids on urinary excretion of Na+ and K+. Since 6-7 reduction of DOCA and 9 alpha-F-Cac substantially reduces affinity for Type II receptors but not Type I receptors, 6-dehydro-derivatives will thus bind preferentially to receptors influencing the retention of sodium (the "mineralocorticoid" or Type I receptor), and compete with mineralocorticoids for such receptors.
View Article and Find Full Text PDFThe rapid compensatory growth seen in the remaining adrenal gland of the rat after unilateral adrenalectomy appears to require a functioning neural arc between the adrenal glands and the hypothalamus, but the role of adrenal or pituitary hormones is unclear. We have examined the effect of several steroids on the compensatory adrenal growth (CAG). Female and male rats (average wt 140 g) were unilaterally adrenalectomized and treated with aldosterone (2.
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