Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect
The aim of this study was to correlate mineralocorticoid action and steroid structure. Inasmuch as Na+ retention follows a parabolic dose-response curve for most pregnanesteroids, the second-order coefficient of the function was used as a representative factor for this bipartite biological effect. T...
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| Autores principales: | , , |
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| Formato: | JOUR |
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00142999_v454_n2-3_p131_PiwienPilipuk |
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| Sumario: | The aim of this study was to correlate mineralocorticoid action and steroid structure. Inasmuch as Na+ retention follows a parabolic dose-response curve for most pregnanesteroids, the second-order coefficient of the function was used as a representative factor for this bipartite biological effect. The C3=O/D angle of the ligands was correlated with both Na+-retaining activity and binding affinity for the mineralocorticoid receptor. Because some steroids exhibit identical functional groups and different conformational structure, we also postulate that the flat conformation of a pregnanesteroid determines its Na+-retaining capacity in vivo. No correlations were found in vitro, which demonstrates the multifactorial nature of the second-order coefficient determined in vivo under more complex and interactive conditions that include various pre-receptor variables. These findings may allow the estimation of the putative biological activity of a given steroid simply by knowing its conformational structure, which may be important for designing compounds in a pharmaceutical setting. © 2002 Elsevier Science B.V. All rights reserved. |
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