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

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.

Keywords

reporter cell lines tibolone estrogen receptors androgen receptor progesterone receptor glucocorticoid receptor mineralocorticoid receptor reporter cell lines.

Domains

Life Sciences [q-bio] Pharmaceutical sciences Life Sciences [q-bio] Human health and pathology Endocrinology and metabolism

Fichier principal

Maudelonde_Table_1.pdf (53.52 Ko)

maudelonde_fig1.ppt (107.5 Ko)

maudelonde_fig2.ppt (77 Ko)

maudelonde_fig3.ppt (128.5 Ko)

maudelonde_fig4.ppt (88 Ko)

maudelonde_fig5.ppt (69 Ko)

maudelonde_fig6.ppt (139 Ko)

tibolonefinalversion0908.pdf (276.93 Ko)

Origin : Files produced by the author(s)

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Origin : Files produced by the author(s)

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https://www.hal.inserm.fr/inserm-00396319

Submitted on : Wednesday, June 17, 2009-3:50:28 PM

Last modification on : Saturday, September 10, 2022-3:53:21 AM

Long-term archiving on: Monday, October 15, 2012-12:31:51 PM

Dates and versions

inserm-00396319 , version 1 (17-06-2009)

Identifiers

HAL Id : inserm-00396319 , version 1
DOI : 10.1016/j.jsbmb.2009.03.008
PUBMED : 19464167

Cite

Aurélie Escande, Nadège Servant, Fanja Rabenoelina, Gilles Auzou, Helenius Kloosterboer, et al.. Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites.. Journal of Steroid Biochemistry and Molecular Biology, 2009, 116 (1-2), pp.8-14. ⟨10.1016/j.jsbmb.2009.03.008⟩. ⟨inserm-00396319⟩

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INSERM FNCLCC VALDAURELLE BS UNIV-MONTPELLIER IRCM

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