Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites.

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Escande A, Servant N, Rabenoelina F, Auzou G, Kloosterboer H, Cavailles V, Balaguer P, Maudelonde T

Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites.

J Steroid Biochem Mol Biol. 2009 Aug;116(1-2):8-14. doi: 10.1016/j.jsbmb.2009.03.008. Epub 2009 Apr 2.

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19464167 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tibolone	Estrogen receptor alpha	Protein	Humans	Yes	Antagonist Agonist	Details