Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites.
Abstract
This work was undertaken (i) to study deeply the estrogen, androgen and progestative activities of tibolone and its metabolites (ii) to determine whether tibolone and its metabolites present glucocorticoid or mineralocorticoid activity. For this purpose, we used human cell lines bearing a luciferase gene with a responsive element under the control of human estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta) or androgen receptor (AR) or chimeric Gal4 fusion with progesterone receptor (PR), glucocorticoid receptor (GR) or mineralocorticoid receptor (MR). The major tibolone metabolites, the two hydroxymetabolites, bind and activate ER with a preference for ERalpha. Tibolone and the Delta(4)-tibolone are agonists for AR and PR and surprisingly 3alpha- and 3beta-OH-tibolone are antagonists for them. Moreover we showed for the first time that tibolone and its primary metabolites are GR and MR antagonists with a stronger affinity for MR than for GR. In conclusion, tibolone by these actions on different receptors and by this capacity to transform in different metabolites, has more complex effects than initially supposed.
Fichier principal
Maudelonde_Table_1.pdf (53.52 Ko)
Télécharger le fichier
maudelonde_fig1.ppt (107.5 Ko)
Télécharger le fichier
maudelonde_fig2.ppt (77 Ko)
Télécharger le fichier
maudelonde_fig3.ppt (128.5 Ko)
Télécharger le fichier
maudelonde_fig4.ppt (88 Ko)
Télécharger le fichier
maudelonde_fig5.ppt (69 Ko)
Télécharger le fichier
maudelonde_fig6.ppt (139 Ko)
Télécharger le fichier
tibolonefinalversion0908.pdf (276.93 Ko)
Télécharger le fichier
Origin : Files produced by the author(s)
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Origin : Files produced by the author(s)