Receptor profiling and endocrine interactions of tibolone

@article{Gooyer2003ReceptorPA,
  title={Receptor profiling and endocrine interactions of tibolone},
  author={Marcel de Gooyer and Godefrides H Deckers and Willem G.E.J. Schoonen and Herman A. M. Verheul and Helenius Jan Kloosterboer},
  journal={Steroids},
  year={2003},
  volume={68},
  pages={21-30}
}
The receptor profiles and in vivo activity of tibolone, and its primary metabolites, Delta(4)-isomer, and 3alpha- and 3beta-hydroxytibolone, were studied and compared to those of structurally related compounds. The Delta(4)-isomer was the strongest binder and activator of the progesterone receptor (PR); tibolone was 10 times weaker in binding and half as potent in transactivation of PR; 3alpha- and 3beta-hydroxytibolone did not bind or activate PR. In rabbits oral tibolone produced a minor… Expand
Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites
TLDR
Tibolone by these actions on different receptors and by this capacity to transform in different metabolites, has more complex effects than initially supposed. Expand
Tibolone and its delta-4, 7α-methyl norethisterone metabolite are reversible inhibitors of human aromatase
TLDR
It is concluded that, in addition to inhibiting STS and 17beta-HSD1, tibolone and 7alpha-MeNET may exert some of their tissue-selective effects in regulating oestrogen synthesis by also inhibiting aromatase activity. Expand
Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue
TLDR
This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients. Expand
Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone
TLDR
It is shown that 5α-dihydrotestosterone (DHT) and Δ(4)-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Expand
Tibolone and its metabolites enhance tissue factor and PAI-1 expression in human endometrial stromal cells: Evidence of progestogenic effects
TLDR
The findings suggest that HESCs metabolize 3alpha- and 3beta-OH tibolone to tibobolone and subsequently to Delta-4 tIBolone, which can both stimulate the progesterone receptor and account for the reduced occurrence of abnormal uterine bleeding associated with tibiaolone therapy. Expand
Regulation of SULT1E1 expression in Ishikawa adenocarcinoma cells by tibolone
TLDR
The results indicate that the lack of endometrial stimulation involves induction of SULT1E1 and the selective sulfation and inactivation of the estrogenic 3-OH tibolones and interconversion of the tIBolone metabolites to generate the progestagenic non-sulfated Delta4-isomer. Expand
Molecular portrait of the progestagenic and estrogenic actions of tibolone: behavior of cellular networks in response to tibolone.
TLDR
The final genetic network analysis indicated that the estrogenic effect of tibolone is potentially counterbalanced by the progestagenic metabolite of tIBolone via differential regulation of similar cellular processes. Expand
Tissue-selectivity: the mechanism of action of tibolone.
TLDR
Tibolone appears to regulate estrogenic activity in the various tissues by influencing the availability of estrogenic compounds for the estradiol receptor in a tissue-selective manner and has direct oestrogenic effects on the cardiovascular system. Expand
Tissue-selective effects of tibolone on the breast.
TLDR
Clinical studies have shown that tibolone users experience less breast tenderness and do not show an increase in mammographic density as found with continuous combined EPT, and the data concerning tibolin and breast cancer risk are inconclusive and require further investigation. Expand
Effects of tibolone on nuclear receptors in human endometrial cells.
TLDR
Tibolone significantly reduced ERalpha in stromal cells and increased PR in glandular cells and these biological effects may play essential roles in averting stimulation of the endometrium in tibolones users. Expand
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