Effects of tibolone on nuclear receptors in human endometrial cells.
OBJECTIVE
Tibolone 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 (ERalpha and ERbeta), progesterone receptor (PR), and androgen receptor (AR) in human endometrial stromal and glandular cells.


METHODS
Human 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).


RESULTS
In endometrial stromal cells, tibolone, Delta4-tibolone, and 3betaOH-tibolone, but not 3alphaOH-tibolone, significantly reduced ERalpha mRNA by approximately 60% and ERalpha protein by approximately 80%. No reduction of ERalpha 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 (approximately 1.5-fold) in stromal cells. Tibolone increased ERbeta and had little effect on AR mRNA in endometrial cells.


CONCLUSIONS
The results showed the majority of the nuclear receptors were not significantly altered. However, tibolone significantly reduced ERalpha 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.
Zhang
Wei
W
Department of Ob/Gyn and Reproductive Medicine, SUNY-Stony Brook, Stony Brook, NY 11794, USA.
Mazella
James
J
Kloosterboer
Helenius J
HJ
Tseng
Linda
L
D015153:Blotting, Western; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009652:Norpregnenes / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects*
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; C027385:tibolone