Effects of tibolone on nuclear receptors in human endometrial cells

ObjectiveTibolone regulates estrogenic activity in a tissue-selective manner. The purpose of this study was to evaluate the effects of tibolone on the mRNA content of nuclear receptors, estrogen receptor-alpha and beta (ERα and ERβ), progesterone receptor (PR), and androgen receptor (AR) in human endometrial stromal and glandular cells.Study designHuman endometrial stromal and glandular cells were isolated from endometrial tissue fragments and separately incubated with tibolone and its metabolites. Nuclear receptor mRNA was determined using real-time polymerase chain reaction (PCR).ResultsIn endometrial stromal cells, tibolone, Δ4-tibolone, and 3βOH-tibolone, but not 3αOH-tibolone, significantly reduced ERα mRNA by ∼60% and ERα protein by ∼80%. No reduction of ERα was observed in endometrial glandular cells. Tibolone induced PR mRNAs to various extents and reached up to 6-fold in glandular cells, but only a moderate increase (∼1.5-fold) in stromal cells. Tibolone increased ERβ and had little effect on AR mRNA in endometrial cells.ConclusionThe results showed the majority of the nuclear receptors were not significantly altered. However, tibolone significantly reduced ERα in stromal cells and increased PR in glandular cells. These biological effects may play essential roles in averting stimulation of the endometrium in tibolone users.