Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.
Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.
Hanifi-Moghaddam
P
P
Department of Reproduction and Development, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Boers-Sijmons
B
B
Klaassens
A H A
AH
van Wijk
F H
FH
den Bakker
M A
MA
Ott
M C
MC
Shipley
G L
GL
Verheul
H A M
HA
Kloosterboer
H J
HJ
Burger
C W
CW
Blok
L J
LJ
D016000:Cluster Analysis; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D004958:Estradiol / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007045:Hysterectomy, Vaginal; D008525:Medroxyprogesterone / Q000009:adverse effects*; D009652:Norpregnenes / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017698:Postmenopause; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014596:Uterine Prolapse / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery
D009652:Norpregnenes; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; C027385:tibolone; D008525:Medroxyprogesterone