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

@article{Escande2009RegulationOA,
  title={Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites},
  author={A. Escande and N. Servant and F. Rabenoelina and G. Auzou and H. Kloosterboer and V. Cavaill{\`e}s and P. Balaguer and T. Maudelonde},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  year={2009},
  volume={116},
  pages={8-14}
}
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… Expand
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References

SHOWING 1-10 OF 49 REFERENCES
Receptor profiling and endocrine interactions of tibolone
TLDR
It is concluded that the progestagenic and androgenic activities of tibolone are mediated by the Delta(4)-isomer, and the estrogenic activity, by the 3-hydroxytibolones. Expand
Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.
TLDR
17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia, and progesterone metabolism to these compounds is a possible protective mechanism for hMR. Expand
Tibolone: a steroid with a tissue-specific mode of action
  • H. Kloosterboer
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2001
TLDR
It is concluded that tibolone acts as a tissue-specific compound by mediating its effects via steroid receptors and enzymatic pathways, and avoids stimulation of the endometrium and breast tissue. Expand
Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolite.
TLDR
Results indicate that 7alpha-Me-EE2 is a very potent estrogenic metabolite of tibolone, and additional studies are, therefore, warranted regarding the role of this metabolite in the biological actions of the drug. Expand
The Synthetic Androgen Methyltrienolone (R1881) Acts as a Potent Antagonist of the Mineralocorticoid Receptor
TLDR
Findings indicate that androgen ligands, particularly R1881, act as MR antagonists in aldosterone target cells and provide new insights into the requirements for MR activation to occur and for the designing of new selective MR antagonists. Expand
Estrogenic effects of 7α-methyl-17α-ethynylestradiol: a newly discovered tibolone metabolite
Abstract Tibolone is a synthetic steroid that is prescribed to postmenopausal women for relief of climacteric symptoms and prevention of osteoporosis. It has been reported to be metabolized in aExpand
Steroid receptor profiling of vinclozolin and its primary metabolites.
TLDR
Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta, and their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process. Expand
Tibolone for postmenopausal women: systematic review of randomized trials.
TLDR
The results from the randomized, controlled, and double blind trials of tibolone are discussed, with respect to its effects on climacteric symptoms, sexual function, endometrial and breast tissue, lipid metabolism, and bone mineral density. Expand
A stable prostatic bioluminescent cell line to investigate androgen and antiandrogen effects
TLDR
It is demonstrated that this stable transfectant provides an accurate tool for studying wild-type human AR activation and its regulation by androgens and antiandrogens in a human prostatic epithelial cell, which is routinely available and remains androgen-responsive in vitro. Expand
A-ring reduced metabolites of 19-nor synthetic progestins as subtype selective agonists for ER alpha.
TLDR
Subtype-selective differences in ligand binding and transcriptional potency of nonphenolic synthetic 19-nor derivatives between ER alpha and ER beta may be useful in evaluating the distinct role of these receptors as well as in providing useful insights into ER action. Expand
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