title: 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.
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, 34298 Montpellier, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Escande
authors.forename: Nadège
authors.initials: N
authors.lastname: Servant
authors.forename: Fanja
authors.initials: F
authors.lastname: Rabenoelina
authors.forename: Gilles
authors.initials: G
authors.lastname: Auzou
authors.forename: Helenius
authors.initials: H
authors.lastname: Kloosterboer
authors.forename: Vincent
authors.initials: V
authors.lastname: Cavaillès
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
mesh_terms: D000728:Androgens; D002460:Cell Line; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009650:Norpregnanes / Q000378:metabolism; D009652:Norpregnenes / Q000378:metabolism / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000819:agonists / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*
chemical_list: C529843:3beta-OH-tibolone; D000728:Androgens; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009650:Norpregnanes; D009652:Norpregnenes; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; C485706:delta(4)-tibolone; D008156:Luciferases; C027385:tibolone