Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.
Hum Reprod
; 23(2): 440-6, 2008 Feb.
Article
in En
| MEDLINE
| ID: mdl-17993476
ABSTRACT
BACKGROUND:
Although uterine leiomyomas or fibroids are the most common gynecological benign tumor and greatly affect reproductive health and well-being, the pathophysiology and epidemiology of uterine leiomyomas are poorly understood. Elevated blood pressure has an independent, positive association with risk for clinically detected uterine leiomyoma. Angiotensin II (Ang II) is a key biological peptide in the renin-angiotensin system that regulates blood pressure.METHODS:
In this study, we investigated the potential role of Ang II (1-1000 nM) in the proliferation of rat ELT-3 leiomyoma cells in vitro. RT-PCR and western blot analysis with cell proliferation and DNA transfection assays were performed to determine the mechanism of action of Ang II.RESULTS:
Ang II induced ELT-3 leiomyoma cell proliferation (P < 0.01) and the expression of Ang II type 1 receptor (AT(1)R) and AT(2)R mRNA and protein was confirmed. Regarding the intracellular signaling pathway, the Ang II-induced cell proliferation was AT(1)R-, epidermal growth factor receptor-, extracellular-regulated kinase- and protein kinase C-dependent but was not dependent on the AT(2)R or phosphatidylinositol-3 kinase or JAK kinase. The AT(1)R blocker telmisartan, effectively repressed Ang II-induced and estradiol-induced cell proliferation (P < 0.01). AT(1)R, but not AT(2)R, plays a role in Ang II-induced ELT-3 cell proliferation.CONCLUSIONS:
These experimental findings in vitro highlight the potential role of Ang II in the proliferation of leiomyoma cells.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uterine Neoplasms
/
Benzimidazoles
/
Benzoates
/
Angiotensin II
/
Angiotensin II Type 1 Receptor Blockers
/
Estradiol
/
Leiomyoma
Limits:
Animals
Language:
En
Journal:
Hum Reprod
Journal subject:
MEDICINA REPRODUTIVA
Year:
2008
Document type:
Article
Affiliation country:
Japan