Sodium-retaining activity of some natural and synthetic 21-deoxysteroids

The effect of progesterone and six other C21 -deoxysteroids on renal sodium retention by male adrenaleotomized rats was compared with the effect exerted by the natural corticoids aldosterone, 11-deoxycorticosterone, and corticosterone. Steroids were active in the following order: aldosterone > 11...

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Detalles Bibliográficos
Autores principales: Burton, G., Galigniana, M., De Lavallaz, S., Brachet-Cota, A.L., Sproviero, E.M., Ghini, A.A., Lantos, C.P., Damasco, M.C.
Formato: JOUR
Materias:
11,19 oxidoprogesterone
11beta,17beta dihydroxy 6 methyl 17alpha (1 propynyl)androsta 1,4,6 trien 3 one
21 deoxycorticosterone
5alpha pregnane 3,20 dione
6,19 oxido 11 oxoprogesterone
6,19 oxidoprogesterone
aldosterone
corticosterone
deoxycorticosterone
mineralocorticoid receptor
pregnanedione
progesterone
progesterone derivative
transcortin
unclassified drug
adrenalectomy
animal experiment
animal tissue
article
controlled study
dose response
drug conformation
drug half life
intramuscular drug administration
intraperitoneal drug administration
male
nonhuman
potassium urine level
priority journal
rat
receptor affinity
sodium retention
sodium urine level
subcutaneous drug administration
Adrenal Glands
Adrenalectomy
Aldosterone
Animal
Comparative Study
Cytosol
Desoxycorticosterone
Half-Life
Kidney
Male
Molecular Conformation
Potassium
Progesterone
Rats
Rats, Sprague-Dawley
Receptors, Steroid
Sodium
Steroids
Support, Non-U.S. Gov't
Tritium
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0026895X_v47_n3_p535_Burton
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:The effect of progesterone and six other C21 -deoxysteroids on renal sodium retention by male adrenaleotomized rats was compared with the effect exerted by the natural corticoids aldosterone, 11-deoxycorticosterone, and corticosterone. Steroids were active in the following order: aldosterone > 11,19-oxidoprogesterone > 5αH-3,20-pregnanedione ≥ 5βH-3,20-pregnanedione > progesterone = 11-ketoprogesterone > 6,19-oxidoprogesterone = 11-keto- 6,19-oxidoprogesterone ≥ corticosterone. All C21-deoxysteroids, except 11,19-oxidoprogesterone, exhibited parabolic log dose-response functions, indicating an effect that opposes renal sodium retention at high doses. 11,19-Oxidoprogesterone and the natural corticoids exhibited normal, exponential, log dose-response curves. Diverse geometric parameters related to molecular planarity were calculated and their correlation with biopharmacological properties was attempted. The best linear regression was obtained for correlation of the concavity of log dose-response parabolas (second-order coefficients) of C21-deoxysteroids with the C3=O/ring D angle of these molecules. A good linear regression could also be obtained for correlation of the affinity of C21-deoxysteroids, except 11,19- oxidoprogesterone, for purified type I mineralocorticoid receptors with those angles. The latter correlation deteriorated upon incorporation of the affinity data for the three natural corticoids, due to similar affinities of these hormones for type I mineralocorticoid receptors, but could be restored when the binding data for the unpurified, corticosterone-binding globulin- containing stage of the receptors were considered. In vivo binding data followed the same trend as that for unpurified receptors.

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