Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.

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.

• Authors: Aki Isobe, Takashi Takeda, Masahiro Sakata, Asako Miyake, Toshiya Yamamoto, Ryoko Minekawa, Fumihito Nishimoto, Yoko Oskamoto, Cheryl Lyn Walker, Tadashi Kimura
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 23 Issue 2 Pg. 440-6 (Feb 2008) ISSN: 1460-2350 [Electronic] England
• PMID: 17993476 (Publication Type: Journal Article)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Angiotensin II
• Estradiol
• Telmisartan

Topics

• Angiotensin II (pharmacology)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Benzoates (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Estradiol (pharmacology)
• Female
• Leiomyoma (chemically induced, metabolism, pathology)
• Rats
• Receptor, Angiotensin, Type 1 (metabolism)
• Receptor, Angiotensin, Type 2 (metabolism)
• Signal Transduction
• Telmisartan
• Uterine Neoplasms (chemically induced, metabolism, pathology)